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Sample records for split-course regimen combining

  1. Accelerated split course regimen in the treatment of brain metastases

    International Nuclear Information System (INIS)

    Franchin, G.; Minatel, E.; Roncadin, M.; Trovo, M.G.; De Paoli, A.; Bortolus, R.; Arcicasa, M.; Boz, G.; Gobitti, C.; Grigoletto, E.; Bassignano, G.

    1988-01-01

    63 patients, with brain metastases were treated with an accelerated split course regimen; irradiation was given to the whole brain in 3 daily fractions of 160 cGy each for 5 days a week. The cycle was repeated after 2 weeks to a total dose of 4800 cGy. Male-female ratio was 3:1. Median age was 58 years. The most frequent site of primary tumor was lung (41 patients), breast in 6 patients, melanoma in 3 patients, other sites in 8 patients and unknown cancer in 5 patients. Thirty-five patients had multiple brain metastases localizations. Two patients failed to complete the scheduled treatment: one because of early death and the other by refusal of therapy during treatment. Complete remission was obtained in 4 patients and partial remission in 24 patients. The median survival time was 21 weeks. The overall response rate was 42.5%. Toxicity was not considerable. The treatment results were not influenced by the site of primary tumor or by disease spreading; only the neurologic status before radiotherapy and the response to treatment influenced survival. The results obtained are similar to those reported by others; however, with the accelerated split course regimen the treatment time was reduced and a shorter period of hospitalization was required. 36 refs.; 2 figs.; 3 tabs

  2. [Combined treatment: regimens, indications and safety profile].

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    Muñiz Grijalvo, Ovidio; Villar Ortiz, Jose

    2013-01-01

    Statins are the current basis of lipid-lowering therapy, despite which may have limitations on efficacy and safety. In high risk patients who do not achieve current lipid goals, in those intolerant to statins or those with atherogenic dyslipidemia, it is possible combine two or more lipid lowering drugs, including statins, ezetimibe, bile acid sequestrants, fibrates, niacin and prescription omega-3 fatty acids. However, for most of these combination therapies pivotal data on clinical outcomes are still lacking. Copyright © 2013 Elsevier España, S.L. and SEA. All rights reserved.

  3. Comparison of split-course radiation therapy and continuous radiation therapy for unresectable bronchogenic carcinoma: 5 year results

    International Nuclear Information System (INIS)

    Lee, R.E.; Carr, D.T.; Childs, D.S. Jr.

    1976-01-01

    One hundred and eighty-eight patients with inoperable or unresectable bronchogenic carcinoma were stratified by cell type, TNM staging, and prior surgery and then randomized into two treatment groups: continuous radiation therapy and split-course radiation therapy. There was no difference in clinical or objective improvement in the two groups. Survival rates for cases of squamous cell carcinoma, small cell carcinoma, and adenocarcinoma were the same after both regimens of therapy. Split-course therapy resulted in a significantly better survival rate in cases of large cell carcinoma but the number of cases was small. We doubt that the difference is clinically significant. Objective roentgenographic response was accompanied by improved survival in squamous cell carcinoma, but not in the other three cell types. Split-course radiation therapy is superior to continuous radiation therapy because it is better tolerated by the patient and because re-examination of the patient prior to the second half of split-course therapy permits the detection of new metastatic disease that has become manifest during the rest period and spares the patient the futile second half of radiation therapy

  4. Split-Course, High-Dose Palliative Pelvic Radiotherapy for Locally Progressive Hormone-Refractory Prostate Cancer

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    Gogna, Nirdosh Kumar, E-mail: kumar_gogna@health.qld.gov.au [Radiation Oncology Services, Mater Centre, Brisbane, Queensland (Australia); Baxi, Siddhartha; Hickey, Brigid; Baumann, Kathryn [Radiation Oncology Services, Mater Centre, Brisbane, Queensland (Australia); Burmeister, Elizabeth [Princess Alexandra Hospital, Brisbane, Queensland (Australia); Holt, Tanya [Radiation Oncology Services, Mater Centre, Brisbane, Queensland (Australia)

    2012-06-01

    Purpose: Local progression, in patients with hormone-refractory prostate cancer, often causes significant morbidity. Pelvic radiotherapy (RT) provides effective palliation in this setting, with most published studies supporting the use of high-dose regimens. The aim of the present study was to examine the role of split-course hypofractionated RT used at our institution in treating this group of patients. Methods and Materials: A total of 34 men with locoregionally progressive hormone-refractory prostate cancer, treated with a split course of pelvic RT (45-60 Gy in 18-24 fractions) between 2000 and 2008 were analyzed. The primary endpoints were the response rate and actuarial locoregional progression-free survival. Secondary endpoints included overall survival, compliance, and acute and late toxicity. Results: The median age was 71 years (range, 53-88). Treatment resulted in an overall initial response rate of 91%, a median locoregional progression-free survival of 43 months, and median overall survival of 28 months. Compliance was excellent and no significant late toxicity was reported. Conclusions: The split course pelvic RT described has an acceptable toxicity profile, is effective, and compares well with other high-dose palliative regimens that have been previously reported.

  5. Rapidly alternating combination of cisplatin-based chemotherapy and hyperfractionated accelerated radiotherapy in split course for Stage IIIA and Stage IIIB non-small cell lung cancer: results of a Phase I-II study by the GOTHA group

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    Alberto, P.; Mermillod, B. [Hopital Cantonal Geneve, Geneva (Switzerland); Mirimanoff, R.O.; Leyvraz, S.; Nagy-Mignotte, H.; Bolla, M.; Wellmann, D.; Moro, D.; Brambilla, E. [Hopital Cantonal Universitaire, Lausanne (Switzerland)

    1995-08-01

    The prognosis of stage III non-small cell lung cancer (NSCLC) can be improved by a combination of radiotherapy (RT) and chemotherapy (CT). In this study, the GOTHA group evaluated the feasibility, tolerance, tumour response, pattern of failure and effect on survival of a combination alternating accelerated hyperfractionated (AH) RT and CT in patients with tumour stage III NSCLC. Toxic effects were leucopenia, nausea and vomiting, mucositis, diarrhoea, alopecia and peripheral neuropathy. Alternating CT and AHRT, as used in this study, were well tolerated and allowed full dose delivery within less than 12 weeks. Initial response was not predictive of survival. The survival curve is encouraging and the 5 year survival is superior to the 5% generally observed with conventionally fractionated radiotherapy. (author).

  6. Efficacy of Some Combination Regimens of Oral Hypoglycaemic ...

    African Journals Online (AJOL)

    Purpose: To examine the efficacy of selected oral hypoglycaemic agent (OHA) regimens in a small group of patients receiving such treatment. Methods: This was a retrospective, observational study that involved patients who had been diagnosed with type 2 diabetes mellitus and undergoing routine follow-up at a teaching ...

  7. Targeted radionuclide therapy in combined-modality regimens.

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    Gill, Martin R; Falzone, Nadia; Du, Yong; Vallis, Katherine A

    2017-07-01

    Targeted radionuclide therapy (TRT) is a branch of cancer medicine concerned with the use of radioisotopes, radiolabelled molecules, nanoparticles, or microparticles that either naturally accumulate in or are designed to target tumours. TRT combines the specificity of molecular and sometimes physical targeting with the potent cytotoxicity of ionising radiation. Targeting vectors for TRT include antibodies, antibody fragments, proteins, peptides, and small molecules. The diversity of available carrier molecules, together with the large panel of suitable radioisotopes with unique physicochemical properties, allows vector-radionuclide pairings to be matched to the molecular, pathological, and physical characteristics of a tumour. Some pairings are designed for dual therapeutic and diagnostic applications. Use of TRT is increasing with the adoption into practice of radium-223 dichloride for the treatment of bone metastases and with the ongoing clinical development of, among others, 177 Lu-dodecanetetraacetic acid tyrosine-3-octreotate (DOTATATE) for the treatment of neuroendocrine tumours and 90 Y-microspheres for the treatment of hepatic tumours. The increasing use of TRT raises the question of how best to integrate TRT into multimodality protocols. Achievements in this area and the future prospects of TRT are evaluated in this Review. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Revisiting Dosing Regimen Using Pharmacokinetic/Pharmacodynamic Mathematical Modeling: Densification and Intensification of Combination Cancer Therapy.

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    Meille, Christophe; Barbolosi, Dominique; Ciccolini, Joseph; Freyer, Gilles; Iliadis, Athanassios

    2016-08-01

    Controlling effects of drugs administered in combination is particularly challenging with a densified regimen because of life-threatening hematological toxicities. We have developed a mathematical model to optimize drug dosing regimens and to redesign the dose intensification-dose escalation process, using densified cycles of combined anticancer drugs. A generic mathematical model was developed to describe the main components of the real process, including pharmacokinetics, safety and efficacy pharmacodynamics, and non-hematological toxicity risk. This model allowed for computing the distribution of the total drug amount of each drug in combination, for each escalation dose level, in order to minimize the average tumor mass for each cycle. This was achieved while complying with absolute neutrophil count clinical constraints and without exceeding a fixed risk of non-hematological dose-limiting toxicity. The innovative part of this work was the development of densifying and intensifying designs in a unified procedure. This model enabled us to determine the appropriate regimen in a pilot phase I/II study in metastatic breast patients for a 2-week-cycle treatment of docetaxel plus epirubicin doublet, and to propose a new dose-ranging process. In addition to the present application, this method can be further used to achieve optimization of any combination therapy, thus improving the efficacy versus toxicity balance of such a regimen.

  9. Radical curative efficacy of tafenoquine combination regimens in Plasmodium cynomolgi-infected Rhesus monkeys (Macaca mulatta

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    Kenworthy David

    2011-07-01

    Full Text Available Abstract Background Tafenoquine is an 8-aminoquinoline being developed for radical cure (blood and liver stage elimination of Plasmodium vivax. During monotherapy treatment, the compound exhibits slow parasite and fever clearance times, and toxicity in glucose-6-phosphate dehydrogenase (G6PD deficiency is a concern. Combination with other antimalarials may mitigate these concerns. Methods In 2005, the radical curative efficacy of tafenoquine combinations was investigated in Plasmodium cynomolgi-infected naïve Indian-origin Rhesus monkeys. In the first cohort, groups of two monkeys were treated with a three-day regimen of tafenoquine at different doses alone and in combination with a three-day chloroquine regimen to determine the minimum curative dose (MCD. In the second cohort, the radical curative efficacy of a single-day regimen of tafenoquine-mefloquine was compared to that of two three-day regimens comprising tafenoquine at its MCD with chloroquine or artemether-lumefantrine in groups of six monkeys. In a final cohort, the efficacy of the MCD of tafenoquine against hypnozoites alone and in combination with chloroquine was investigated in groups of six monkeys after quinine pre-treatment to eliminate asexual parasites. Plasma tafenoquine, chloroquine and desethylchloroquine concentrations were determined by LC-MS in order to compare doses of the drugs to those used clinically in humans. Results The total MCD of tafenoquine required in combination regimens for radical cure was ten-fold lower (1.8 mg/kg versus 18 mg/kg than for monotherapy. This regimen (1.8 mg/kg was equally efficacious as monotherapy or in combination with chloroquine after quinine pre-treatment to eliminate asexual stages. The same dose of (1.8 mg/kg was radically curative in combination with artemether-lumefantrine. Tafenoquine was also radically curative when combined with mefloquine. The MCD of tafenoquine monotherapy for radical cure (18 mg/kg appears to be biologically

  10. Analysis of combination drug therapy to develop regimens with shortened duration of treatment for tuberculosis.

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    George L Drusano

    Full Text Available Tuberculosis remains a worldwide problem, particularly with the advent of multi-drug resistance. Shortening therapy duration for Mycobacterium tuberculosis is a major goal, requiring generation of optimal kill rate and resistance-suppression. Combination therapy is required to attain the goal of shorter therapy.Our objective was to identify a method for identifying optimal combination chemotherapy. We developed a mathematical model for attaining this end. This is accomplished by identifying drug effect interaction (synergy, additivity, antagonism for susceptible organisms and subpopulations resistant to each drug in the combination.We studied the combination of linezolid plus rifampin in our hollow fiber infection model. We generated a fully parametric drug effect interaction mathematical model. The results were subjected to Monte Carlo simulation to extend the findings to a population of patients by accounting for between-patient variability in drug pharmacokinetics.All monotherapy allowed emergence of resistance over the first two weeks of the experiment. In combination, the interaction was additive for each population (susceptible and resistant. For a 600 mg/600 mg daily regimen of linezolid plus rifampin, we demonstrated that >50% of simulated subjects had eradicated the susceptible population by day 27 with the remaining organisms resistant to one or the other drug. Only 4% of patients had complete organism eradication by experiment end.These data strongly suggest that in order to achieve the goal of shortening therapy, the original regimen may need to be changed at one month to a regimen of two completely new agents with resistance mechanisms independent of the initial regimen. This hypothesis which arose from the analysis is immediately testable in a clinical trial.

  11. Weekly taxane-anthracycline combination regimen versus tri-weekly anthracycline-based regimen for the treatment of locally advanced breast cancer: a randomized controlled trial.

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    Tan, Qiu-Wen; Luo, Ting; Zheng, Hong; Tian, Ting-Lun; He, Ping; Chen, Jie; Zeng, He-Lin; Lv, Qing

    2017-03-07

    Extensive studies have confirmed the efficacy of taxanes in combination with anthracycline-based chemotherapy on breast cancer. However, few studies have assessed the efficacy of weekly taxane-anthracycline regimens on locally advanced breast cancer. This study was to compare the efficacy and safety of a weekly taxane-anthracycline regimen with those of tri-weekly anthracycline-based regimen in patients with locally advanced breast cancer. Patients with locally advanced breast cancer were randomized to receive 4-6 cycles of neoadjuvant chemotherapy with tri-weekly 5-fluorouracil-epirubicin-cyclophosphamide (FEC) regimen or weekly paclitaxel-epirubicin (PE) regimen. The primary endpoint was the pathologic complete response (pCR) rate. Other endpoints included the clinical tumor response, breast-conserving surgery rate, and adverse events. Between March 2010 and September 2013, 293 patients were randomized to the FEC (n = 151) and PE (n = 142) arms. The overall clinical response rate was significantly higher in the PE arm than in the FEC arm (76.06% vs. 59.95%, P = 0.001). Consistently, the post-chemotherapy pathologic T and N stages were significantly lower in the PE arm than in the FEC arm (P breast-conserving surgery. Most adverse events were comparable in both arms, with more severe neutropenia in the PE arm than in the FEC arm (11.97% vs. 5.96%, P = 0.031). In patients with locally advanced breast cancer, weekly PE was not superior to FEC in terms of pCR. However, weekly PE has a higher response rate and superior down-staging effects. On this account, the PE regimen may be considered an alternative option for locally advanced breast cancer. Long-term follow-up data are needed to confirm the efficacy of this regimen on locally advanced breast cancer. Trial registration Chinese clinical trial registry, ChiCTR-TRC-10001043, September 21, 2014.

  12. New regimens with combined oral contraceptive pills--moving away from traditional 21/7 cycles.

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    Read, Christine M

    2010-12-01

    The practice of extending combined oral contraceptive use (COC) and eliminating or reducing the hormone free interval has been in use for many years. More recently a range of products with new dosing options has been developed and marketed. Women and physicians in developed countries are comfortable with and many prefer the use of extended COC regimens which provide an option to eliminate or reduce the frequency of regular withdrawal bleeding. The extension of active pill taking and the reduction or elimination of the hormone-free interval have been shown to be beneficial for women who experience menstrual cycle-related problems such as heavy bleeding or dysmenorrhoea. The hormone-free interval of less than seven days has additional benefits in managing hormone withdrawal symptoms and efficacy may be improved in situations where pills are inadvertently missed or in women who are perceived as 'poor' pill takers. This paper provides a descriptive review highlighting the development of new dosing options that alter the traditional 21/7 COC regimen. The rationale for and the acceptability of COCs developed with alternative dosing regimens is examined.

  13. Nanoparticle delivery of chemotherapy combination regimen improves the therapeutic efficacy in mouse models of lung cancer.

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    Tian, Jing; Min, Yuangzeng; Rodgers, Zachary; Wan, Xiaomeng; Qiu, Hui; Mi, Yu; Tian, Xi; Wagner, Kyle T; Caster, Joseph M; Qi, Yanfei; Roche, Kyle; Zhang, Tian; Cheng, Jianjun; Wang, Andrew Z

    2017-04-01

    The combination chemotherapy regimen of cisplatin (CP) and docetaxel (DTX) is effective against a variety of cancers. However, combination therapies present unique challenges that can complicate clinical application, such as increases in toxicity and imprecise exposure of tumors to specific drug ratios that can produce treatment resistance. Drug co-encapsulation within a single nanoparticle (NP) formulation can overcome these challenges and further improve combinations' therapeutic index. In this report, we employ a CP prodrug (CPP) strategy to formulate poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) NPs carrying both CPP and DTX. The dually loaded NPs display differences in drug release kinetics and in vitro cytotoxicity based on the structure of the chosen CPP. Furthermore, NPs containing both drugs showed a significant improvement in treatment efficacy versus the free drug combination in vivo. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Alternative temozolomide dosing regimens and novel combinations for the treatment of advanced metastatic melanoma

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    Wen-Jen Hwu

    2011-12-01

    Full Text Available Over the past 30 years, there has been no significant improvement in treatment outcomes for patients with advanced stage IV metastatic melanoma, and prognosis remains poor. Melanoma is known to be responsive to immunomodulatory agents, to be a highly vascular tumor, and to be fairly resistant to standard cytotoxic chemotherapy. Ongoing research is attempting to find novel combinations that may have therapeutic synergy. Alternative dosedense schedules of temozolomide appear promising and are being actively investigated, based on their potential to overcome chemoresistance to alkylating agents and the proven activity of temozolomide in the brain. Outcomes of studies investigating single-agent temozolomide suggest that it has activity similar to single-agent dacarbazine. Other studies combining temozolomide with either interferon- alfa or thalidomide suggest that the addition of these immunomodulatory agents to temozolomide improves response rates and may improve overall survival. The best results have been achieved with the extended, daily, dosedense temozolomide regimen. Further research is needed to determine the optimal temozolomide regimen and best combination approach

  15. Comparison of clinical efficacy between decitabine combined with half the amount of CAG regimen with CAG regimen alone in patients with inermediate to high-risk myelodysplastic syndrome

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    Fan Zhenwei

    2017-01-01

    Full Text Available Objective: To investigate the efficacy and safety of decitabine combined with half the amount of CAG and CAG regimen alone. Methods: Comparison the effectiveness, overall survival and incidence of adverse reactions of 42 cases of MDS used decitabine combined with half the amount of CAG regimen (decitabine 20mg/m2, once a day, d1-3, Accra neomycin 7mg/m2,intravenous injection, once a day, d4-7, cytarabine 10mg/m2, every 12 hours, d4-10, granulocyte colony stimulating factor 300μg, once a day, d4-10, white blood cell count>20×109/L when deactivated for four courses and 48 patients in MDS were treated with chemotherapy alone CAG (Accra neomycin 14mg/m2,once a day, d1-3, cytarabine 10mg/m2, every 12 hours, d1-14, granulocyte colony stimulating factor 300μg, once a day, d1-14, white blood cell count>20×109/L when deactivated. Results: Compared with pure CAG, clinical efficacy of decitabine combined with half the amount of CAG regimen is better, the treatment does not increase the risk.

  16. Clinical observation and therapeutic evaluation of Rh-endostatin combined with DP regimen in treating patients with advanced esophageal cancer.

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    Deng, Wen-Ying; Song, Tao; Li, Ning; Luo, Su-Xia; Li, Xiang

    2014-01-01

    To observe the curative effects of rh-endostatin combined with DP regimen in treating patients with advanced esophageal cancer and analyze the correlation of CT perfusion (CTP) parameters and the expression of vascular endothelial growth factor (VEGF). Twenty patients with esophageal cancer confirmed pathologically were randomly divided into combined treatment (rh-endostatin+DP regimen) group and single chemotherapy group, 10 patients in each group, respectively. All patients were given conventional CT examination and CTP imaging for primary tumor. The level of VEGF, the size of tumor and CTP parameters (BF, BV, PS and MTT) before treatment and after 2 cycles of treatment were determined for the comparison and the correlation between CTP parameters and VEGF expression was analyzed. the therapeutic effect of rh-endostatin+DP regimen group was superior to single chemotherapy group. VEGF level after treatment in rh- endostatin +DP regimen group was obviously lower than single chemotherapy group (Prh-endostatin +DP regimen group, BF, BV and PS decreased while MTT increased after treatment (P0.05). Rh-endostatin can down-regulate the expression of VEGF in esophageal cancer, change the state of hypertransfusion and high permeability of tumor vessels and had the better curative effect and slighter adverse reactions when combined with chemotherapy.

  17. Cardiovascular effects of Phaleria macrocarpa extracts combined with mainstay FAC regimen for breast cancer.

    Science.gov (United States)

    Anggadiredja, Kusnandar; Tjandrawinata, Raymond R

    2015-01-01

    DLBS1425 is a bioactive compound extracted from Phaleria macrocarpa, with anti-proliferative, anti-inflammatory and anti-angiogenic properties against cancer cells. The present study was aimed to assess cardiotoxicity of DLBS1425, compared to the mainstay regimen for breast cancer, 5-fluorouracil:doxorubicin:cyclophosphamide (FAC, given at 500/50/500 mg/m(2)). Treatment with FAC regimen at standard dose resulted in very severe toxicity, so mice had no chance to survive for more than 7 days following initial drug treatment. Furthermore, histological examination on the heart revealed severe muscular damage when mice were given the FAC regimen alone (severe toxicity). FAC as chemotherapeutic regimen exerted high toxicity profile to the cardiovascular cells in this experiment. Meanwhile, treatment with DLBS1425 alone up to a dose equivalent to as high as 300 mg three times daily in human had no hazardous consequences on the heart, hematological feature, as well as general safety. In the cardiovascular cells, DLBS1425 in the presence of FAC regimen (one-eight of the initial dose) gave protection to the cardiac muscle cells as well as other hematological features. Taken together, results of the present study suggest that DLBS1425 is safe when used as adjuvant therapy for breast cancer and may be even protective against cardiac cellular damage produced by chemotherapeutic regimen.

  18. Comparison of the safety and efficacy of a fixed-dose combination regimen and separate formulations for pulmonary tuberculosis treatment

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    Jiun-Ting Wu

    2015-06-01

    Full Text Available OBJECTIVES: Fixed-dose combination formulations, which simplify the administration of drugs and prevent the development of drug resistance, have been recommended as a standard anti-tuberculosis treatment regimen. However, the composition and dosage recommendations for fixed-dose combination formulations differ from those for separate formulations. Thus, questions about the effectiveness and side effects of combination formulations remain. The aim of this study was to compare the safety and efficacy of these two types of anti-tuberculosis regimens for pulmonary tuberculosis treatment. METHOD: A prospective, randomized controlled study was conducted using the directly observed treatment short-course strategy. Patients were randomly allocated to one of two short-course regimens. One year after completing the treatment, these patients’ outcomes were analyzed. ClinicalTrials.gov: NCT00979290. RESULTS: A total of 161 patients were enrolled, 142 of whom were evaluable for safety assessment. The two regimens had a similar incidence of adverse effects. In the per-protocol population, serum bilirubin concentrations at the peak level, at week 4, and at week 8 were significantly higher for the fixed-dose combination formulation than for the separate formulations. All patients had negative sputum cultures at the end of the treatment, and no relapse occurred after one year of follow-up. CONCLUSIONS: In this randomized study, transient higher serum bilirubin levels were noted for the fixed-dose combination regimen compared with the separate formulations during treatment. However, no significant difference in safety or efficacy was found between the groups when the directly observed treatment short-course strategy was used.

  19. Efficacy of a combined contraceptive regimen consisting of condoms and emergency contraception pills.

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    Zhao, Rui; Wu, Jun-Qing; Li, Yu-Yan; Zhou, Ying; Ji, Hong-Lei; Li, Yi-Ran

    2014-04-14

    To evaluate and compare the effectiveness of the combined regimen (consisting of condoms and emergency contraception pills (ECP)) and using condoms only for the purpose of preventing pregnancy. One-thousand-five-hundred-and-sixty-two (1,562) couples as volunteers enrolled at nine centers in Shanghai. Eight-hundred-and-twelve (812) were randomized to use male condoms and ECP (i.e., Levonorgestrel) as a back-up to condoms (the intervention group) and 750 to use male condoms only(the control group), according to their working unit. Participants were visited at admission and at the end of 1, 3, 6, 9, and 12 months. The cumulative life table rates were calculated for pregnancy and other reasons for discontinuation. The gross cumulative life table rates showed that the cumulative discontinuation rates for all reasons during the year of follow-up in the condoms plus emergency contraception group and the condoms only group were 7.76 ± 0.94 and 6.61 ± 0.91, respectively, per 100 women (χ2 = 0.41, p = 0.5227). The cumulative gross pregnancy rate of the condoms plus emergency contraception group and the condoms only group were 2.17 ± 0.52 and 1.25 ± 0.41, respectively, per 100 women (χ2 = 1.93, p = 0.1645). The Pearl Index in the condoms plus emergency contraception group and the condoms only group were 2.21% and 1.26%, respectively. Male condoms remain a highly effective contraceptive method for a period of one year while consistently and correctly used. In addition, the lowest pregnancy rate followed from perfect use condom.

  20. Treatment of 29 patients with bulky squamous cell carcinoma of the cervix with simultaneous cisplatin, 5-fluorouracil, and split-course hyperfractionated radiation therapy

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    Heaton, D.; Yordan, E.; Reddy, S.; Bonomi, P.; Lee, M.S.; Lincoln, S.; Graham, J.; Dolan, T.; Miller, A.; Phillips, A. (Rush Presbyterian-St. Lukes Hospital, Chicago, IL (USA))

    1990-09-01

    Attempting to improve local disease control in bulky primary or recurrent pelvic tumors, 29 patients with squamous cell carcinoma of the cervix were treated with concomitant chemotherapy and split-course hyperfractionated radiation therapy between April 1983 and August 1988. Cisplatin (CDDP) and 5-fluorouracil (5-FU) have been shown to be radiation enhancers; furthermore, CDDP, radiation therapy, and continuous-infusion 5-FU have elicited high local response rates in head and neck squamous cell carcinoma. A pilot study of cyclical week on/week off CDDP, continuous-infusion 5-FU, and hyperfractionated radiation therapy was developed. Radiation was administered at 116 cGy twice daily, Days 1-5, every other week for a median dose of 4600 cGy to a pelvic field, with paraaortic extension if indicated. Concomitant chemotherapy included CDDP 60 mg/m2 IV Day 1 and 5-FU 600 mg/m2 IV continuous infusion for 96 hr following CDDP infusion. Patients received a median of four cycles of combined treatment, and intracavitary or interstitial brachytherapy followed in 21 patients. Local pelvic response was achieved in 29 of 29 (100%): complete response (CR) in 19 of 29 (66%), partial response (PR) in 10 of 29 (34%). Among CR patients 10 of 19 (53%) were without evidence of disease at a mean follow-up of 29 (range 12-76) months. Five-year actuarial disease-free survival among complete responders was 65%. Of the 10 CR patients 2 failed in the pelvis, for a local control rate of 17/19 (89%). Chemotherapy-related and acute radiation morbidity was minimal but 2 patients required surgical correction of radiation injury. Aggressive combination of split-course hyperfractionated radiation therapy with radiation enhancers resulted in promising local control of bulky pelvic tumor, with an acceptable complication rate, in this otherwise very poor prognostic group of patients.

  1. Efficacy and tolerance of artemisinin in short combination regimens for the treatment of uncomplicated falciparum malaria

    NARCIS (Netherlands)

    Bich, N. N.; de Vries, P. J.; van Thien, H.; Phong, T. H.; Hung, L. N.; Eggelte, T. A.; Anh, T. K.; Kager, P. A.

    1996-01-01

    Two oral regimens comprising a single dose of 20 mg/kg of artemisinin followed by three days of quinine, 10 mg/kg three times a day (AQ), or doxycycline, 4 mg/kg once a day (AD), were compared with a standard seven-day course of oral quinine, 10 mg/kg three times a day (Q), in the treatment of

  2. Split-course accelerated therapy in head and neck cancer: an analysis of toxicity

    International Nuclear Information System (INIS)

    Delaney, Geoffrey P.; Fisher, Richard J.; Smee, Robert I.; Hook, Carolyn; Barton, Michael B.

    1995-01-01

    Purpose: To retrospectively assess a protocol of split-course accelerated radiation therapy (SCAT) for selected head and neck cancers. Methods and Materials: SCAT consisted of 1.8 Gy per fraction administered twice daily with a minimum gap between fractions of 6 h. The treatment protocol prescribed an initial 16 fractions followed by a planned 5 to 12 day break, and then a further 20 to 22 fractions for a total dose ranging from 64.8 to 72 Gy delivered in 5 to 6 weeks. Results: Twenty-eight patients received SCAT for histologically confirmed head and neck cancer between January 1987 and August 1991. All patients were followed up until December 1, 1993. The mean potential follow-up time was 4.2 years (range: 2.9-6.2 years). All patients completed the treatment protocol. Thirteen tumors were laryngeal in origin, eight hypopharyngeal, four paranasal sinus, and three oropharyngeal. There were no Stage I, three Stage II, nine Stage III, and 12 Stage IV tumors. Four tumors were not staged (two paranasal sinus cancers and two surgical recurrences). Early and late toxicities were moderate to severe. Confluent mucositis was experienced by 27 of the 28 patients (96%). One patient required a prolonged midtreatment break of 24 days. Nine patients (32%) required narcotic analgesia for pain relief. Eleven patients (39%) required hospitalization for nasogastric feeding or pain control. The median length of hospital stay was 14 days (range 7-98 days). The actuarial rate of severe late toxicity at 3 years was 47% (standard error (SE) = 13%). A complete tumor response was achieved in 86% of patients. The actuarial local control rate at 3 years was 43% (SE = 11%) and the actuarial survival rate at 3 years was 25% (SE = 8%). Conclusion: Given the encouraging complete response rate and local control for such advanced tumors, SCAT for locoregionally advanced tumors merits further investigation. However, because of the significant late toxicity observed, the total dose, interfraction

  3. A meta-analysis of hyperfractionated and accelerated radiotherapy and combined chemotherapy and radiotherapy regimens in unresected locally advanced squamous cell carcinoma of the head and neck

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    Budach V

    2006-01-01

    Full Text Available Abstract Background Former meta-analyses have shown a survival benefit for the addition of chemotherapy (CHX to radiotherapy (RT and to some extent also for the use of hyperfractionated radiation therapy (HFRT and accelerated radiation therapy (AFRT in locally advanced squamous cell carcinoma (SCC of the head and neck. However, the publication of new studies and the fact that many older studies that were included in these former meta-analyses used obsolete radiation doses, CHX schedules or study designs prompted us to carry out a new analysis using strict inclusion criteria. Methods Randomised trials testing curatively intended RT (≥60 Gy in >4 weeks/>50 Gy in Results Thirty-two trials with a total of 10 225 patients were included into the meta-analysis. An overall survival benefit of 12.0 months was observed for the addition of simultaneous CHX to either CFRT or HFRT/AFRT (p Conclusion RT combined with simultaneous 5-FU, cisplatin, carboplatin, and mitomycin C as single drug or combinations of 5-FU with one of the other drugs results in a large survival advantage irrespective the employed radiation schedule. If radiation therapy is used as single modality, hyperfractionation leads to a significant improvement of overall survival. Accelerated radiation therapy alone, especially when given as split course radiation schedule or extremely accelerated treatments with decreased total dose, does not increase overall survival.

  4. Efficacy and acceptability of a mifepristone-misoprostol combined regimen for early induced abortion among women in Mexico City.

    Science.gov (United States)

    Peña, Melanie; Dzuba, Ilana G; Smith, Patricio Sanhueza; Mendoza, Luis Jorge Arellano; Bousiéguez, Manuel; Martínez, María Laura García; Polanco, Ranulfo Ríos; Villalón, Antonio Eduardo Flores; Winikoff, Beverly

    2014-10-01

    To evaluate the experience of women receiving mifepristone-misoprostol for early induced abortion in public sector facilities in the Federal District of Mexico City. An open-label prospective study was conducted with 1000 pregnant women who sought induced abortion with a pregnancy of up to 63days of gestation, as measured from the date of their last menstrual period. The study was conducted in three public sector healthcare facilities: two secondary level hospitals and one primary care clinic. Women ingested 200mg mifepristone on day 1, followed by 800μg buccal misoprostol 24hours later, and they returned for follow-up on day 8. The primary outcome was complete abortion without recourse to surgical intervention. A total of 971 women received mifepristone-misoprostol and were included in the analysis for efficacy of treatment. The overall efficacy of the combined medical abortion regimen studied was 97.3% (n=945); the success rate did not vary significantly by gestational age (95.9%-100%; P=0.449). Most women (n=922, 95.0%) had a successful induced abortion with only one dose of misoprostol. The combined mifepristone and buccal misoprostol regimen was found to be highly effective and acceptable among Mexican women. www.ClinicalTrials.gov: NCT00386282. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  5. [Efficacy of PVD regimen combined with IMRT for early-stage extranodal nasal NK/T-cell lymphoma].

    Science.gov (United States)

    Zhang, Y; Huang, Y H; Hu, Y F; Liu, Q L; Wu, T

    2017-07-11

    Objective: To evaluate the efficacy of PVD chemo-regimen (Pegaspargase, vincristine and dexamethasone) combined with intensity-modulated radiotherapy (IMRT) for patients with early-stage extranodal nasal NK/T-cell lymphoma (ENKL). Methods: Clinical data of 52 patients with early-stage ENKL were collected during May 2010 and June 2015 in Department of Lymphoma, Cancer Hospital of Guizhou Medical University, and these patients firstly received a concurrent chemoradiotherapy of two-cycle of PVD and IMRT (gross tumor volume primary: 12.6-59.4 Gy) and then 2 to 4 cycles of PVD as subsequent chemotherapy, the efficacy and adverse responses were retrospectively analyzed and observed. Results: Follow-up stopped until December 2015, complete remission was seen in 44 cases (84.6%) and partial remission 7 cases (13.5%), out of 52 cases. A total of 1 case died of progression disease during treatment and within 1 year after treatment, 1 case died of pulmonary infection within 1 week after treatment, 2 cases survived with tumor; so the objective response rate and clinical benefit rate were both 98.1%, 1-year, 2-year and 3-year overall survival rates and progression free survival rates were all 93.6%, 1-year and 2-year disease free survival rates were both 90.3%; the correlation analysis showed that the radiotherapy dose was related to the curative effect ( P PVD regimen and IMRT have a good therapeutic effect and adverse response can be tolerated.

  6. A randomized trial comparing initial HAART regimens of nelfinavir/nevirapine and ritonavir/saquinavir in combination with two nucleoside reverse transcriptase inhibitors

    DEFF Research Database (Denmark)

    Kirk, Ole; Lundgren, Jens D; Pedersen, Court

    2003-01-01

    BACKGROUND: A triple-class HAART regimen may be associated with a better virological effect than conventional regimens, but may also lead to toxicity and more profound resistance. METHODS: Randomized, controlled, open-label trial of 233 protease inhibitor- and non-nucleoside reverse transcriptase...... inhibitor-naive HIV-infected patients allocated to a regimen of nelfinavir and nevirapine (1250/200 mg twice daily; n = 118) or ritonavir and saquinavir (400/400 mg twice daily; n = 115), both in combination with two nucleoside reverse transcriptase inhibitors. The primary end-point was HIV RNA ....037. CONCLUSION: A regimen of nelfinavir/nevirapine had a favourable virological effect and tolerability over a 48-week period compared with ritonavir/saquinavir, when administered in combination with two nucleoside reverse transcriptase inhibitors. However, more extensive follow-up is required to determine...

  7. Combining vascular and cellular targeting regimens enhances the efficacy of photodynamic therapy

    International Nuclear Information System (INIS)

    Chen Bin; Pogue, Brian W.; Hoopes, P. Jack; Hasan, Tayyaba

    2005-01-01

    Purpose: Photodynamic therapy (PDT) can be designed to target either tumor vasculature or tumor cells by varying the drug-light interval. Photodynamic therapy treatments with different drug-light intervals can be combined to increase tumor response by targeting both tumor vasculature and tumor cells. The sequence of photosensitizer and light delivery can influence the effect of combined treatments. Methods and materials: The R3327-MatLyLu rat prostate tumor model was used in this study. Photosensitizer verteporfin distribution was quantified by fluorescence microscopy. Tumor blood flow changes were monitored by laser-Doppler system and tumor hypoxia was quantified by the immunohistochemical staining for the hypoxic marker EF5. The therapeutic effects of PDT treatments were evaluated by the histologic examination and tumor regrowth assay. Results: Fluorescence microscopic studies indicated that tumor localization of verteporfin changed from predominantly within the tumor vasculature at 15 min after injection, to being throughout the tumor parenchyma at 3 h after injection. Light treatment (50 J/cm 2 ) at 15 min after verteporfin injection (0.25 mg/kg, i.v.) induced significant tumor vascular damage, as manifested by tumor blood flow reduction and increase in the tumor hypoxic fraction. In contrast, the vascular effect observed after the same light dose (50 J/cm 2 ) delivered 3 h after administration of verteporfin (1 mg/kg, i.v.) was an initial acute decrease in blood flow, followed by recovery to the level of control. The EF5 staining revealed no significant increase in hypoxic fraction at 1 h after PDT using 3 h drug-light interval. The combination of 3-h interval PDT and 15-min interval PDT was more effective in inhibiting tumor growth than each individual PDT treatment. However, it was found that the combined treatment with the sequence of 3-h interval PDT before 15-min interval PDT led to a superior antitumor effect than the other combinative PDT treatments

  8. Viral replication under combination antiretroviral therapy: A comparison of four different regimens

    NARCIS (Netherlands)

    Ghani, Azra C.; Ferguson, Neil M.; Fraser, Christophe; Donnelly, Christl A.; Danner, Sven; Reiss, Peter; Lange, Joep; Goudsmit, Jaap; Anderson, Roy M.; de Wolf, Frank

    2002-01-01

    A mathematical model of the interaction among CD4(+) T-cells, HIV-1, and antiretroviral drugs was fitted to the viral load decline following initiation of combination therapy to estimate differences in the residual reproductive capacity of virus (R-0) in the average patient in each group. Four

  9. Immunotherapy regimens for combination with photodynamic therapy aimed at eradication of solid cancers

    Science.gov (United States)

    Korbelik, Mladen

    2000-06-01

    Due to inflammatory/immune responses elicited by photodynamic therapy (PDT), this modality is particularly suitable in combination with various forms of immunotherapy for an improved therapeutic gain. A wide variety of approaches that may be applicable in this context include those focusing on amplifying the activity of particular immune cell types (neutrophils, macrophages, dendritic cells, natural killer cells, helper or cytotoxic T lymphocytes). Another type of approach is to focus on a specific phase of immune response development, which comprises the activation of non-specific inflammatory immune effectors, immune recognition, immune memory, immune rejection, or blocking of immune suppression. These different strategies call for a variety of immunotherapeutic protocols to be employed in combination with PDT. These include treatments such as: (1) non-specific immunoactivators (e.g. bacterial vaccines), (2) specific immune agents (cytokines, or other activating factors), (3) adoptive immunotherapy treatments (transfer of dendritic cells, tumor-sensitized T lymphocytes or natural killer cells), or (4) their combinations. Techniques of gene therapy employed in some of these protocols offer novel opportunities for securing a potent and persistent immune activity. Using PDT and immunotherapy represents an attractive combination for cancer therapy that is capable of eradicating both localized and disseminated malignant lesions.

  10. Continuous and split-course radiotherapy in locally advanced carcinoma of the uterine cervix. Analyses of local control, distant metastases, crude survival, early and late morbidity and prognostic factors

    International Nuclear Information System (INIS)

    Pedersen, D.E.

    1994-01-01

    From 1974 to 1984, 442 consecutive patients with carcinoma of the uterine cervix were referred for combined intracavitary (IRT) and external radiotherapy (ERT). Dose prescriptions were performed based on the points A and B of the Manchester system. From 1978 the treatment strategy was changed from continuous (CRT) to split course radiotherapy (SCRT) with a higher total dose to point B, a lower dose to point A from the IRT, and a longer total treatment time (TTT). The purpose of the present thesis is: To evaluate local tumour control, distant metastases, survival and complications in the rectosigmoid and bladder in relation to treatment strategy (continuous and split course radiotherapy). To evaluate prognostic factors and importance of treatment strategy for local control, distant metastases, and survival by uni- and multivariate analyses. To develop a classification system (AADK, Aarhus, Denmark) for the recording of early and late radiation complications allowing and estimation of the importance of latency when reporting late radiotherapeutic morbidity and a rescoring of complication grade, and to compare results from AADK with those from the French-Italian glossary recording the maximal damage. To evaluate early and late radiotherapeutic morbidity and the importance of latency by comparing frequencies and actuarial estimates of late complications, to estimate the combined late organ morbidity and the probability of being alive, cured and without serious complications. (EG) (61 refs.)

  11. Feasibility of using lower doses of chemopreventive agents in a combination regimen for cancer protection.

    Science.gov (United States)

    Ip, C

    1988-04-01

    In experimental cancer chemoprevention studies, the doses of the agent used to produce an inhibitory response are generally very high, sometimes bordering on levels that will result in toxicity to the test animals. The present study was designed to test the hypothesis that low doses of two or more agents may be just as effective as high doses of a single agent. An earlier report from our laboratory showed that vitamin E, although ineffective by itself, potentiates the anti-carcinogenic potency of selenite. Our objective was to complete a comprehensive set of dose titration experiments in the quantitative analysis of the synergism between selenium (Se) and vitamin E. Results indicated that the minimal amount of vitamin E required was around 500 ppm, which when combined with as little as 1 ppm Se, produced a significant protective effect in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumor model. This level of Se is 5 times below the marginal toxicity level of 5 ppm observed in our previous experience. With a 3-agent combination protocol involving Se (1 ppm), vitamin E (500 ppm) and vitamin A (66 ppm), it was found that vitamin A at this particular dose did not contribute any further chemoprevention than that provided by the Se/vitamin E duo. Both Se and vitamin E were present at a concentration 10 times, while vitamin A was present at 30 times their respective nutritional requirement. Our findings thus suggest that the minimum effective dose has to be systematically established for each micronutrient, and that it is feasible to use lower doses of a combination of agents if the threshold level of each agent can be determined under a prescribed set of conditions.

  12. Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimen

    DEFF Research Database (Denmark)

    Cozzi-Lepri, Alessandro; Phillips, Andrew N; Ruiz, Lidia

    2007-01-01

    OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points...

  13. An outpatient regimen of combined oral mifepristone 400 mg and misoprostol 400 microg for first-trimester legal medical abortion

    DEFF Research Database (Denmark)

    Ravn, Pernille; Rasmussen, Ase; Knudsen, Ulla Breth

    2005-01-01

    AIM: To evaluate the success rate of medical abortion using an outpatient regimen of oral mifepristone 400 mg and oral misoprostol 400 microg for legal abortion in women ... ultrasound and minimal vaginal bleeding at a control examination performed 14 days after administration of misoprostol. Over a 6-month period in 2003, a questionnaire (completion rate 70%) was used for a spot check of the patients' evaluation of the method. RESULTS: Six hundred and sixty women underwent...... abortion again in case of a future unwanted pregnancy, and 85% would prefer to abort at home again. CONCLUSION: A high acceptance and success rate was seen using this outpatient oral regimen of mifepristone and misoprostol....

  14. Comparison of adherence to generic multi-tablet regimens vs. brand multi-tablet and brand single-tablet regimens likely to incorporate generic antiretroviral drugs by breaking or not fixed-dose combinations in HIV-infected patients.

    Science.gov (United States)

    Rwagitinywa, Joseph; Lapeyre-Mestre, Maryse; Bourrel, Robert; Montastruc, Jean-Louis; Sommet, Agnès

    2018-03-05

    Adherence to antiretroviral (ARV) is crucial to achieve viral load suppression in HIV-infected patients. This study aimed to compare adherence to generic multi-tablet regimens (MTR) vs. brand MTR likely to incorporate ARV drugs without breaking fixed-dose combinations (FDC) and brand single-tablet regimens (STR) likely to incorporate generics by breaking the FDC. Patients aged of 18 years or over exposed to one of the generic or the brand of lamivudine (3TC), zidovudine/lamivudine (AZT/TC), nevirapine (NVP), or efavirenz (EFV), or the brand STR of efavirenz/emtricitabine/tenofovir (EFV/FTC/TDF). Adherence was measured by medication possession ratio (MPR) using both defined daily dose (DDD) and daily number of tablet recommended for adults (DNT). Adherence to generic MTR vs. brand MTR and brand STR was compared using Kruskal-Wallis. The overall median adherence was 0.97 (IQR 0.13) by DNT method and 0.97 (0.14) by DDD method. Adherence in patients exposed to generic MTR (n = 165) vs. brand MTR (n = 481) and brand STR (n = 470) was comparable by DNT and DDD methods. In conclusion, adherence to generic MTR was high and comparable with adherence to brand MTR and to STR. Utilization of DDD instead DNT to measure the MPR led to small but nonsignificant difference that has no clinical impact. © 2018 Société Française de Pharmacologie et de Thérapeutique.

  15. Split-course radiation therapy of carcinoma of the nasopharynx: results of a national collaborative clinical trial of the Radiation Therapy Oncology Group

    International Nuclear Information System (INIS)

    Marcial, V.A.; Hanley, J.A.; Chang, C.; Davis, L.W.; Moscol, J.A.

    1980-01-01

    The initial results of a prospective randomized collaborative therapeutic trial of split-course radiotherapy in carcinoma of the nasopharynx are reported. The split-course therapy consisted of two irradiation courses, each delivering 3000 rad in 2 weeks, in 10 fractions of 300 rad. The courses were separated by a rest period of 3 weeks. Continuous radiation therapy consisted of 30 fractions of 220 rad each, for a total dose of 6600 rad. One hundred and nine patients were eligible for analysis with a minimal follow-up period of 1 year. No statistically significant differences were observed in the two therapeutic groups with regard to acute toxicity (normal tissue reactions, completion of therapy, and need of hospitalization during radiotherapy), late toxicity, incidence of distant metastases, patients who became free of clinically detectable tumor in the primary and neck sites at last follow-up or at death, and survival after therapy

  16. Treatment outcomes of fixed-dose combination versus separate tablet regimens in pulmonary tuberculosis patients with or without diabetes in Qatar.

    Science.gov (United States)

    Al-Shaer, Mohammad H; Mansour, Hanine; Elewa, Hazem; Salameh, Pascale; Iqbal, Fatima

    2017-02-02

    Tuberculosis is considered the second most common cause of death due to infectious agent. The currently preferred regimen for treatment of pulmonary tuberculosis (PTB) is isoniazid, rifampin, pyrazinamide, and ethambutol, which has been used either as separate tablets (ST) or as fixed-dose combination (FDC). To date, no studies have compared both regimens in Qatar. We aim to evaluate the safety and effectiveness of FDC and ST regimen for treating PTB, in addition to comparing safety and efficacy of FDC and ST regimens in patients with diabetes treated for TB. A retrospective observational study was conducted in two general hospitals in Qatar. Patients diagnosed with PTB received anti-tuberculosis medications (either as FDC or ST) administered by the nurse. Sputum smears were tested weekly. We assessed the time to negative sputum smear and incidence of adverse events among FDC and ST groups. The study included 148 patients. FDC was used in 90 patients (61%). Effectiveness was not different between FDC and ST regimens as shown by mean time to sputum conversion (29.9 ± 18.3 vs. 35.6 ± 23 days, p = 0.12). Similarly, there was no difference in the incidence of adverse events, except for visual one that was higher in ST group. Among the 33 diabetic patients, 19 received the FDC and had faster sputum conversion compared to those who received ST (31 ± 12 vs. 49.4 ± 30.9 days, p = 0.05). Overall, diabetic patients needed longer time for sputum conversion and had more hepatotoxic and gastric adverse events compared to non-diabetics. ST group had higher visual side effects compared to FDC. FDC may be more effective in diabetic patients; however, further studies are required to confirm such finding.

  17. Incidence of virological failure and major regimen change of initial combination antiretroviral therapy in the Latin America and the Caribbean: an observational cohort study

    Science.gov (United States)

    Cesar, Carina; Jenkins, Cathy A.; Shepherd, Bryan E.; Padgett, Denis; Mejía, Fernando; Ribeiro, Sayonara Rocha; Cortes, Claudia P.; Pape, Jean W.; Madero, Juan Sierra; Fink, Valeria; Sued, Omar; McGowan, Catherine; Cahn, Pedro

    2015-01-01

    Background Access to combination antiretroviral therapy (cART) is expanding in Latin America and the Caribbean (LAC). There is little information in this region regarding incidence of and factors associated with regimen failure and regimen change. Methods Antiretroviral-naïve adults starting cART from 2000-2014 at sites in seven countries throughout LAC were included. Cumulative incidence of virologic failure and major regimen change were estimated with death considered a competing event. Findings 14,027 cART initiators (60% male, median age 37 years, median CD4 156 cells/mm3, median HIV-RNA 5·0 log10 copies/mL, and 28% with clinical AIDS) were followed for a median of 3·9 years. 1,719 patients presented virologic failure and 1,955 had a major regimen change. Excluding GHESKIO-Haiti (which did not regularly measure HIV-RNA), cumulative incidence of virologic failure was 7·8%, 19·2%, and 25·8% at one, three, and five years after cART initiation, respectively; cumulative incidence of major regimen change was 5·9%, 12·7%, and 18·2%. Incidence of major regimen change at GHESKIO-Haiti at five years was 10·7%. Virologic failure was associated with younger age (adjusted hazard ratio[aHR]=2·03 for 20 vs. 40 years; 95% confidence interval[CI] 1·68-2·44), infection through injection-drug use (IDU) (aHR=1·60; 95%CI 1·02-2·52), initiation in earlier calendar years (aHR=1·28 for 2002 vs. 2006; 95%CI 1·13-1·46), and starting with a boosted protease inhibitor (aHR=1·17 vs. non-nucleoside reverse transcriptase inhibitor; 95%CI 1·00-1·64). Interpretation Incidence of virologic failure was generally lower than in North America/Europe. Our results suggest the need to design strategies to reduce failure and major regimen change among younger patients and those with a history of IDU. Funding US National Institutes of Health: U01 AI069923. PMID:26520929

  18. Therapeutic Assessment of Chloroquine-Primaquine Combined Regimen in Adult Cohort of Plasmodium vivax Malaria from Primary Care Centres in Southwestern India.

    Directory of Open Access Journals (Sweden)

    Kavitha Saravu

    Full Text Available Several reports of chloroquine treatment failure and resistance in Plasmodium vivax malaria from Southeast Asian countries have been published. Present study was undertaken to assess the efficacy of chloroquine-primaquine (CQ-PQ combined regimen for the treatment of P. vivax malaria patients who were catered by the selected primary health centres (PHCs of Udupi taluk, Udupi district, Karnataka, India.Five PHCs were selected within Udupi taluk based on probability proportional to size. In-vivo therapeutic efficacy assessment of CQ (1500 mg over three days plus PQ (210 mg over 14 days regimen was carried out in accordance with the World Health Organization's protocol of 28 days follow-up among microscopically diagnosed monoinfection P. vivax cohort.In total, 161 participants were recruited in the study of which, 155 (96.3% participants completed till day 28 follow-up, fully complied with the treatment regimen and showed adequate clinical and parasitological response. Loss to follow up was noted with 5 (3.1% participants and non-compliance with treatment regimen occurred with one participant (0.6%. Glucose-6-phosphate dehydrogenase deficiency (G6PDd, <30% of normal mean activity was noted among 5 (3.1% participants and one of them did develop PQ induced dark-brown urination which subsided after PQ discontinuation. G6PDd patients were treated with PQ 45 mg/week for eight weeks while PQ was discontinued in one case with G6PD 1.4 U/g Hb due to complaint of reddish-brown coloured urine by 48 hours of PQ initiation. Nested polymerase chain reaction test revealed 45 (28% cases as mixed (vivax and falciparum malaria.The CQ-PQ combined regimen remains outstandingly effective to treat uncomplicated P. vivax malaria in Udupi taluk and thus it should continue as first line regimen. For all P. vivax cases, G6PD screening before PQ administration must be mandatory and made available in all PHCs.

  19. Comparison of rates of and charges from pregnancy complications in users of extended and cyclic combined oral contraceptive (COC) regimens: a brief report.

    Science.gov (United States)

    Howard, Brandon; Trussell, James; Grubb, ElizaBeth; Lage, Maureen J

    2014-05-01

    To evaluate pregnancy complication rates and related charges in users of 84/7, 21/7 and 24/4 combined oral contraceptives (COCs). Data were obtained from the i3 InVision Data Mart™ retrospective claims database. Subjects were aged 15-40 years, first prescribed a COC between 1/1/2006 and 4/1/2011 and continuously insured for ≥1 year. 84/7 users were matched 1:1 to 21/7 and 24/4 users. Pregnancy-related complication rates and associated charges were significantly lower with 84/7 vs. 21/7 and 24/4 regimens. Preliminary data suggest 84/7 regimens may be associated with fewer pregnancy complications and lower related charges. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Randomised controlled trial of two sequential artemisinin-based combination therapy regimens to treat uncomplicated falciparum malaria in African children: a protocol to investigate safety, efficacy and adherence

    DEFF Research Database (Denmark)

    Schallig, Henk D. F. H.; Tinto, Halidou; Sawa, Patrick

    2017-01-01

    Background Management of uncomplicated Plasmodium falciparum malaria relies on artemisinin-based combination therapies (ACTs). These highly effective regimens have contributed to reductions in malaria morbidity and mortality. However, artemisinin resistance in Asia and changing parasite...... susceptibility to ACT in Africa have now been well documented. Strategies that retain current ACT as efficacious treatments are urgently needed. Methods We present an open-label, randomised three-arm clinical trial protocol in three African settings representative of varying malaria epidemiology to investigate...... whether prolonged ACT-based regimens using currently available formulations can eliminate potentially resistant parasites. The protocol investigates whether a sequential course of two licensed ACT in 1080 children aged 6–120 months exhibits superior efficacy against acute P. falciparum malaria and non...

  1. High-Dose Split-Course Radiation Therapy for Anal Cancer: Outcome Analysis Regarding the Boost Strategy (CORS-03 Study)

    International Nuclear Information System (INIS)

    Hannoun-Levi, Jean-Michel; Ortholan, Cecile; Resbeut, Michel; Teissier, Eric; Ronchin, Philippe; Cowen, Didier; Zaccariotto, Audrey; Benezery, Karen; Francois, Eric; Salem, Naji; Ellis, Steve; Azria, David; Gerard, Jean-Pierre

    2011-01-01

    Purpose: To retrospectively assess the clinical outcome in anal cancer patients treated with split-course radiation therapy and boosted through external-beam radiation therapy (EBRT) or brachytherapy (BCT). Methods and Materials: From January 2000 to December 2004, a selected group (162 patients) with invasive nonmetastatic anal squamous cell carcinoma was studied. Tumor staging reported was T1 = 31 patients (19%), T2 = 77 patients (48%), T3 = 42 patients (26%), and T4= 12 patients (7%). Lymph node status was N0-1 (86%) and N2-3 (14%). Patients underwent a first course of EBRT: mean dose 45.1 Gy (range, 39.5-50) followed by a boost: mean dose 17.9 Gy (range, 8-25) using EBRT (76 patients, 47%) or BCT (86 patients, 53%). All characteristics of patients and tumors were well balanced between the BCT and EBRT groups. Results: The mean overall treatment time (OTT) was 82 days (range, 45-143) and 67 days (range, 37-128) for the EBRT and BCT groups, respectively (p < 0.001). The median follow-up was 62 months (range, 2-108). The 5-year cumulative rate of local recurrence (CRLR) was 21%. In the univariate analysis, the prognostic factors for CRLR were as follows: T stage (T1-2 = 15% vs. T3-4 = 36%, p = 0.03), boost technique (BCT = 12% vs. EBRT = 33%, p = 0.002) and OTT (OTT <80 days = 14%, OTT ≥80 days = 34%, p = 0.005). In the multivariate analysis, BCT boost was the unique prognostic factor (hazard ratio = 0.62 (0.41-0.92). In the subgroup of patients with OTT <80 days, the 5-year CRLR was significantly increased with the BCT boost (BC = 9% vs. EBRT = 28%, p = 0.03). In the case of OTT ≥80 days, the 5-year CRLR was not affected by the boost technique (BCT = 29% vs. EBRT = 38%, p = 0.21). Conclusion: In anal cancer, when OTT is <80 days, BCT boost is superior to EBRT boost for CRLR. These results suggest investigating the benefit of BCT boost in prospective trials.

  2. Incidence of virological failure and major regimen change of initial combination antiretroviral therapy in the Latin America and the Caribbean: an observational cohort study.

    Science.gov (United States)

    Cesar, Carina; Jenkins, Cathy A; Shepherd, Bryan E; Padgett, Denis; Mejía, Fernando; Ribeiro, Sayonara Rocha; Cortes, Claudia P; Pape, Jean W; Madero, Juan Sierra; Fink, Valeria; Sued, Omar; McGowan, Catherine; Cahn, Pedro

    2015-11-01

    Access to combination antiretroviral therapy (ART) is expanding in Latin America (Mexico, Central America, and South America) and the Caribbean. We assessed the incidence of and factors associated with regimen failure and regimen change of initial ART in this region. This observational cohort study included antiretroviral-naive adults starting ART from 2000 to 2014 at sites in seven countries throughout Latin America and the Caribbean. Primary outcomes were time from ART initiation until virological failure, major regimen modification, and a composite endpoint of the first of virological failure or major regimen modification. Cumulative incidence of the primary outcomes was estimated with death considered a competing event. 14,027 patients starting ART were followed up for a median of 3.9 years (2.0-6.5): 8374 (60%) men, median age 37 years (IQR 30-44), median CD4 count 156 cells per μL (61-253), median plasma HIV RNA 5.0 log10 copies per mL (4.4-5.4), and 3567 (28%) had clinical AIDS. 1719 (12%) patients had virological failure and 1955 (14%) had a major regimen change. Excluding the site in Haiti, which did not regularly measure HIV RNA, cumulative incidence of virological failure was 7.8% (95% CI 7.2-8.5) 1 year after ART initiation, 19.2% (18.2-20.2) at 3 years, and 25.8% (24.6-27.0) at 5 years; cumulative incidence of major regimen change was 5.9% (5.3-6.4) at 1 year, 12.7% (11.9-13.5) at 3 years, and 18.2% (17.2-19.2) at 5 years. Incidence of major regimen change at the site in Haiti was 10.7% (95% CI 9.7-11.6) at 5 years. Virological failure was associated with younger age (adjusted hazard ratio [HR] 2.03, 95% CI 1.68-2.44, for 20 years vs 40 years), infection through injection drug use (vs infection through heterosexual sex; 1.60, 1.02-2.52), and initiation in earlier calendar years (1.28, 1.13-1.46, for 2002 vs 2006), but was not significantly associated with boosted protease inhibitor-based regimens (vs non-nucleoside reverse transcriptase inhibitor; 1

  3. Monitoring of Circulating Tumor Cells and Their Expression of EGFR/Phospho-EGFR During Combined Radiotherapy Regimens in Locally Advanced Squamous Cell Carcinoma of the Head and Neck

    Energy Technology Data Exchange (ETDEWEB)

    Tinhofer, Ingeborg, E-mail: ingeborg.tinhofer@charite.de [Translational Radiooncology Laboratory, Department of Radiooncology and Radiotherapy, Charite Campus Mitte, Charite Universitaetsmedizin Berlin, Berlin (Germany); Hristozova, Tsvetana; Stromberger, Carmen [Translational Radiooncology Laboratory, Department of Radiooncology and Radiotherapy, Charite Campus Mitte, Charite Universitaetsmedizin Berlin, Berlin (Germany); KeilhoIz, Ulrich [Department of Hematology and Oncology, Campus Benjamin Franklin, Charite Universitaetsmedizin Berlin, Berlin (Germany); Budach, Volker [Translational Radiooncology Laboratory, Department of Radiooncology and Radiotherapy, Charite Campus Mitte, Charite Universitaetsmedizin Berlin, Berlin (Germany)

    2012-08-01

    Purpose: The numbers of circulating tumor cells (CTCs) and their expression/activation of epidermal growth factor receptor (EGFR) during the course of combined chemo- or bioradiotherapy regimens as potential biomarkers of treatment efficacy in squamous cell carcinoma of the head and neck (SCCHN) were determined. Methods and Materials: Peripheral blood samples from SCCHN patients with locally advanced stage IVA/B disease who were treated with concurrent radiochemotherapy or induction chemotherapy followed by bioradiation with cetuximab were included in this study. Using flow cytometry, the absolute number of CTCs per defined blood volume as well as their expression of EGFR and its phosphorylated form (pEGFR) during the course of treatment were assessed. Results: Before treatment, we detected {>=}1 CTC per 3.75 mL blood in 9 of 31 patients (29%). Basal expression of EGFR was detected in 100% and pEGFR in 55% of the CTC+ cases. The frequency of CTC detection was not influenced by induction chemotherapy. However, the number of CTC+ samples significantly increased after radiotherapy. This radiation-induced increase in CTC numbers was less pronounced when radiotherapy was combined with cetuximab compared to its combination with cisplatin/5-fluorouracil. The former treatment regimen was also more effective in reducing pEGFR expression in CTCs. Conclusions: Definitive radiotherapy regimens of locally advanced SCCHN can increase the number of CTCs and might thus contribute to a systemic spread of tumor cells. Further studies are needed to evaluate the predictive value of the radiation-induced increase in CTC numbers and the persistent activation of the EGFR signalling pathway in individual CTC+ cases.

  4. Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimen

    DEFF Research Database (Denmark)

    Cozzi-Lepri, Alessandro; Phillips, Andrew N; Ruiz, Lidia

    2007-01-01

    (t0 and t1) when viral load was > 400 copies/ml. METHODS: Accumulation of resistance between t0 and t1 was measured using genotypic susceptibility scores (GSS) obtained by counting the total number of active drugs (according to the Rega system v6.4.1) among all licensed antiretrovirals as of 1...... to the failing regimen were still receiving benefit from treatment. An overall 6-monthly increase of 1.96 (SD, 2.23) International Aids Society-mutations and an average loss of 1.25 (SD, 1.81) active drugs were estimated. In comparison with patients with GSS_f-t0 = 0, the number of active drugs lost was -1...

  5. Declining in efficacy of a three-day combination regimen of mefloquine-artesunate in a multi-drug resistance area along the Thai-Myanmar border

    Directory of Open Access Journals (Sweden)

    Ruengweerayut Kulaya

    2010-10-01

    Full Text Available Abstract Background Declining in clinical efficacy of artesunate-mefloquine combination has been documented in areas along the eastern border (Thai-Cambodian of Thailand. In the present study, the clinical efficacy of the three-day combination regimen of artesunate-mefloquine as first-line treatment for acute uncomplicated falciparum malaria in Thailand was monitored in an area along the western border (Thai-Myanmar of the country. Methods A total of 150 Burmese patients (85 males and 65 females aged between 16 and 50 years who were attending the Mae Tao clinic, Mae-Sot, Tak Province, and presenting with symptomatic acute uncomplicated Plasmodium falciparum malaria were included into the study. Patients were treated initially (day 0 with 4 mg/kg body weight artesunate and 15 mg/kg body weight mefloquine. The dose regimen on day 2 was 4 mg/kg body weight artesunate and 10 mg/kg body weight mefloquine. On day 3, artesunate at the dose of 4 mg/kg body weight was given with 0.6 mg/kg body weight primaquine. Whole blood mefloquine and plasma artesunate and dihydroartemisinin (active plasma metabolite of artesunate concentrations following treatment were determined by high performance liquid chromatography (HPLC and liquid chromatography-mass spectrometry (LCMS, respectively. Results Thirty-four cases had recrudescence during days 7 and 42. Five and 5 cases, respectively had reinfection with P. falciparum and reappearance of Plasmodium vivax in their peripheral blood during follow-up. The Kaplan-Meier estimate of the 42-and 28-day efficacy rates of this combination regimen were 72.58% (95% CI: 63.20-79.07% and 83.06 (95% CI 76.14-94.40%, respectively. Parasite clearance time (PCT and fever clearance time (FCT were significantly prolonged in patients with treatment failure compared with those with sensitive response [median (95% CI values for PCT 32.0 (20.0-48.0 vs 24.0 (14.0-32.0 hr and FCT 30.0 (22.0-42.0 vs 26.0 (18.0-36.0 hr; p vs 525 (452-599 ng

  6. The impact of gap duration on local control in anal canal carcinoma treated by split-course radiotherapy and concomitant chemotherapy

    International Nuclear Information System (INIS)

    Weber, Damien C.; Kurtz, John M.; Allal, Abdelkarim S.

    2001-01-01

    Purpose: To investigate the potential benefit of reducing the intersequence gap in patients with anal cancer treated with split-course chemoradiotherapy. Methods: The study group consisted of 90 patients with anal squamous carcinoma treated between 1981 and 1998, using concomitant chemotherapy (CT) and radiation (RT). Median age was 65 years (range 41-87). RT was delivered in a split course, with a median gap of 37.5 days (range 4-97) between sequences. First (pelvic) sequence delivered a median dose of 40 Gy (range 36-50.4), using AP/PA megavoltage photon beams. Boost treatment (median dose 20 Gy, range 13-26) consisted of either Iridium-192 implantation (49 patients) or external beam RT (41 patients). CT consisted of 1-2 cycles of a 5-day continuous infusion of 5-fluorouracil and bolus mitomycin C, usually administered during the first week of each RT course. Median follow-up was 76.2 months. Univariate and multivariate analyses were performed to determine the factors associated with locoregional control (LRC). Results: Five-year actuarial LRC was 72.5%. Factors associated with poorer LRC (univariate) were: age ≤65, male gender, and gap >37.5 days. Number of CT cycles (1 vs. 2 or more), boost technique (brachytherapy vs. external), and T-stage were not significantly associated with LRC. In multivariate analysis, only age (p=0.01), and gap (p=0.02) retained their significance. In patients older than 65 years, LRC was 92.3% and 75% for shorter and longer gaps, respectively. In younger patients, the corresponding values for LRC were 73.7% and 50%. Conclusion: In anal cancers, split-course RT with >50 Gy dose delivery is difficult to avoid because of acute toxicity. The present analysis suggests that shortening the gap contributes to optimizing LRC. Gaps longer than 5 weeks correlated with poorer LRC, with especially unsatisfactory results observed in younger patients

  7. Endometrial carcinoma in vitro chemosensitivity testing of single and combination chemotherapy regimens using the novel microculture kinetic apoptosis assay: implications for endometrial cancer treatment.

    Science.gov (United States)

    Ballard, Karen S; Homesley, Howard D; Hodson, Charles; Presant, Cary A; Rutledge, James; Hallquist, Allan; Perree, Mathieu

    2010-03-01

    The in vitro microculture kinetic (MiCK) apoptosis assay has been used to predict single or combination chemotherapy response in leukemia patients. This feasibility study addressed MiCK in endometrial cancer specimens. Endometrial cancer specimens from total abdominal hysterectomies were processed at a central laboratory. Single cell suspensions of viable endometrial cancer cells were plated in individual wells. Single and combination regimens were tested: combinations of doxorubicin, cisplatin, and paclitaxel and carboplatin and paclitaxel (Gynecologic Oncology Group [GOG] 209 endometrial cancer phase III trial arms) as well as single agent testing with paclitaxel, carboplatin, doxorubicin, cisplatin, ifosfamide, and vincristine (active agents in GOG trials). Apoptosis was measured continuously over 48 hours. Fifteen of nineteen patients had successful assays. The highest mean chemo sensitivity was noted in the combination of cisplatin, doxorubicin, and paclitaxel with lower mean chemosensitivity for carboplatin and paclitaxel. Combination chemotherapy had higher chemosensitivity than single drug chemotherapy. However, in 25% of patients a single drug had higher chemosensitivity than combination chemotherapy. As single agents, ifosfamide, cisplatin, and paclitaxel had the highest kinetic unit values. Using a panel of agents simulating clinical dose regimens, the MiCK assay was feasible in evaluating in vitro chemosensitivity of endometrial cancer. MiCK assay results correlated with GOG clinical trial results. However, 25% of patients might be best treated with single agent chemotherapy selected by MiCK. Ifosfamide, cisplatin, and paclitaxel appear to have high activity as single agents. MiCK may be useful in future new drug testing and individualizing endometrial cancer patient's chemotherapy management.

  8. A study of an effective sunitinib–chemotherapeutic combination regimen for bladder cancer treatment using a mouse model

    Directory of Open Access Journals (Sweden)

    Dah-Shyong Yu

    2014-06-01

    Conclusion: Combination of the tyrosine kinase receptor inhibitor sunitinib with gemcitabine chemotherapy synergistically enhances tumor cytotoxicity and may provide a new treatment modality for advanced bladder cancer.

  9. Safety and efficacy of short course combination regimens with AmBisome, miltefosine and paromomycin for the treatment of visceral leishmaniasis (VL) in Bangladesh.

    Science.gov (United States)

    Rahman, Ridwanur; Goyal, Vishal; Haque, Rashidul; Jamil, Kazi; Faiz, Abul; Samad, Rasheda; Ellis, Sally; Balasegaram, Manica; Boer, Margriet den; Rijal, Suman; Strub-Wourgaft, Nathalie; Alves, Fabiana; Alvar, Jorge; Sharma, Bhawna

    2017-05-01

    AmBisome therapy for VL has an excellent efficacy and safety profile and has been adopted as a first-line regimen in Bangladesh. Second-line treatment options are limited and should preferably be given in short course combinations in order to prevent the development of resistant strains. Combination regimens including AmBisome, paromomycin and miltefosine have proved to be safe and effective in the treatment of VL in India. In the present study, the safety and efficacy of these same combinations were assessed in field conditions in Bangladesh. The safety and efficacy of three combination regimens: a 5 mg/kg single dose of AmBisome + 7 subsequent days of miltefosine (2.5 mg/kg/day), a 5 mg/kg single dose of AmBisome + 10 subsequent days of paromomycin (15 mg/kg/day) and 10 days of paromomycin (15 mg/kg/day) + miltefosine (2.5 mg/kg/day), were compared with a standard regimen of AmBisome 15 mg/kg given in 5 mg/kg doses on days 1, 3 and 5. This was a phase III open label, individually randomized clinical trial. Patients from 5 to 60 years with uncomplicated primary VL were recruited from the Community Based Medical College Bangladesh (CBMC,B) and the Upazila Health Complexes of Trishal, Bhaluka and Fulbaria (all located in Mymensingh district), and randomly assigned to one of the treatments. The objective was to assess safety and definitive cure at 6 months after treatment. 601 patients recruited between July 2010 and September 2013 received either AmBisome monotherapy (n = 158), AmBisome + paromomycin (n = 159), AmBisome + miltefosine (n = 142) or paromomycin + miltefosine (n = 142). At 6 months post- treatment, final cure rates for the intention-to-treat population were 98.1% (95%CI 96.0-100) for AmBisome monotherapy, 99.4% (95%CI 98.2-100) for the AmBisome + paromomycin arm, 94.4% (95%CI 90.6-98.2) for the AmBisome + miltefosine arm, and 97.9% (95%CI 95.5-100) for paromomycin + miltefosine arm. There were 12 serious adverse events in the study in 11 patients that

  10. Cost-Utility of a Single-Injection Combined Corticosteroid-Hyaluronic Acid Formulation vs a 2-Injection Regimen of Sequential Corticosteroid and Hyaluronic Acid Injections.

    Science.gov (United States)

    Belzile, Etienne L; Deakon, Robert T; Vannabouathong, Christopher; Bhandari, Mohit; Lamontagne, Martin; McCormack, Robert

    2017-01-01

    Research has shown early and sustained relief with a combination therapy of a corticosteroid (CS) and hyaluronic acid (HA) in knee osteoarthritis (OA) patients. This can be administered via a single injection containing both products or as separate injections. The former may be more expensive when considering only product cost, but the latter incurs the additional costs and time of a second procedure. The purpose of this study was to compare the cost-utility of the single injection with the 2-injection regimen. The results of this analysis revealed that the single-injection formulation of a CS and HA may be cost-effective, assuming a willingness-to-pay of $50 000 per quality-adjusted life year gained, for symptomatic relief of OA symptoms. This treatment may also be more desirable to patients who find injections to be inconvenient or unpleasant.

  11. Combined bedtime insulin--daytime sulphonylurea regimen compared with two different daily insulin regimens in type 2 diabetes: effects on HbA1c and hypoglycaemia rate--a randomised trial

    NARCIS (Netherlands)

    Stehouwer, M. H. A.; DeVries, J. H.; Lumeij, J. A. E.; Adèr, H. J.; Engbers, A. M. S.; Iperen Av, A. van; Snoek, F. J.; Heine, R. J.

    2003-01-01

    BACKGROUND: Several efficacy studies of insulin-therapy regimens in patients with type 2 diabetes mellitus have shown varying results. Moreover, most studies did not address hypoglycaemia frequency and severity. METHODS: In this multicentre study, we compared the glycaemic efficacy and incidence

  12. Comparative effects of combination drug therapy regimens commencing with either losartan potassium, an angiotensin II receptor antagonist, or enalapril maleate for the treatment of severe hypertension.

    Science.gov (United States)

    Ruff, D; Gazdick, L P; Berman, R; Goldberg, A I; Sweet, C S

    1996-02-01

    To compare the efficacy and safety of a regimen of losartan potassium (losartan) and a regimen of enalapril maleate (enalapril) in a randomized trial of patients with severe hypertension in which the initial treatments were blinded. Seventy-five patients, 23-74 years of age, with sitting diastolic blood pressure of 115-130mmHg, were enrolled in a 12-site multicenter study. The primary efficacy parameters were the change in trough systolic and diastolic blood pressure, as well as response to treatment in terms of categories of hypertensive response. A gradual reduction in mean sitting diastolic blood pressure was observed in all patients treated from week 1 to 12 (10-29mmHg for the losartan regimen and 14-32 mmHg for the enalapril regimen). At week 4, a substantial number of patients remained on monotherapy at either the initial dose or double the dose of losartan (52%) or enalapril (72%). The blood pressure curves for each treatment were parallel over time. The enalapril-based regimen elicited a statistically significantly greater reduction in blood pressure than the losartan-based regimen, although the mean differences in the blood pressure response between the two treatment groups was small. Based on sitting diastolic blood pressure < 90 mmHg or a reduction in blood pressure of at least 10 mmHg, 98% of the patients assigned to the losartan regimen and 100% of the patients assigned to the enalapril regimen had a satisfactory response with a regimen of one to three antihypertensive drugs. Headache was the most common adverse experience in both treatment groups (occurring in 22% of patients assigned to the losartan regimen and 20% of patients assigned to the enalapril regimen). In this study, the losartan-based regimen effectively lowered blood pressure, was generally well tolerated, and was generally similar to the enalapril-based regimen in the treatment of patients with severe hypertension.

  13. Papilla preservation technique combined with Emdogain in the treatment of intrabony defects: a novel treatment regimen for chronic periodontitis.

    Science.gov (United States)

    Miliauskaite, Asta; Selimovic, Denis; Hassan, Mohamed; Nagano, Futami; Soell, Martine; Sano, Hidehiko; Puriene, Alina

    2008-01-01

    Regenerative therapy with enamel matrix proteins derivative (EMD) was shown to induce periodontal regeneration in intrabony defects. However, the contribution of papilla preservation technique (PPT), to the clinical outcome of regenerative therapy is still not clarified. Therefore, we conducted the present study to evaluate clinically measurable results of a combined therapy by PPT and EMD in the treatment of isolated intrabony defects. Sixty isolated intrabony defects in 25 patients were surgically assessed with EMD and PPT. The clinical parameters: clinical attachment level (CAL), probing depth (PD) and gingival recession (GR) were evaluated at baseline and at three years. The primary outcome variable was CAL. The sites treated with enamel matrix proteins demonstrated mean CAL change from 6.6+/-1.2 mm to 3.4+/-1.3 mm (p<0.001) and the mean PD was reduced from 5.9+/-1.0 mm to 2.7+/-0.8 mm (p<0.001) after three years. The mean GR decreased from 0.71+/-1.2 mm to 0.64+/-1.1 mm (p<0.821). The results of the present case cohort study indicate that PPT combined with EMD resulted in significant improvement of the clinical parameters in the treatment of intrabony defects in chronic periodontitis.

  14. Combined regimen of photodynamic therapy mediated by Gallium phthalocyanine chloride and Metformin enhances anti-melanoma efficacy.

    Directory of Open Access Journals (Sweden)

    Diana Tudor

    Full Text Available Melanoma therapy is challenging, especially in advanced cases, due to multiple developed tumor defense mechanisms. Photodynamic therapy (PDT might represent an adjuvant treatment, because of its bimodal action: tumor destruction and immune system awakening. In this study, a combination of PDT mediated by a metal substituted phthalocyanine-Gallium phthalocyanine chloride (GaPc and Metformin was used against melanoma. The study aimed to: (1 find the anti-melanoma efficacy of GaPc-PDT, (2 assess possible beneficial effects of Metformin addition to PDT, (3 uncover some of the mechanisms underlining cell killing and anti-angiogenic effects.Two human lightly pigmented melanoma cell lines: WM35 and M1/15 subjected to previous Metformin exposure were treated by GaPc-PDT. Cell viability, death mechanism, cytoskeleton alterations, oxidative damage, were assessed by means of colorimetry, flowcytometry, confocal microscopy, spectrophotometry, ELISA, Western Blotting.GaPc proved an efficient photosensitizer. Metformin addition enhanced cell killing by mechanisms dependent on the cell line, namely apoptosis in the metastatic M1/15 and necrosis in the radial growth phase, WM35. Cell death mechanism relied on the inhibition of nuclear transcription factor (NF-κB activation and tumor necrosis factor (TNF-related apoptosis-inducing ligand (TRAIL sensitization, leading to TRAIL and TNF-α induced apoptosis. Metformin diminished the anti-angiogenic effect of PDT.Metformin addition to GaPc-PDT increased tumor cell killing through enhanced oxidative damage and induction of proapoptotic mechanisms, but altered PDT anti-angiogenic effects.Combination of Metformin and PDT might represent a solution to enhance the efficacy, leading to a potential adjuvant role of PDT in melanoma therapy.

  15. A phase IIb trial of vorinostat in combination with lenalidomide and dexamethasone in patients with multiple myeloma refractory to previous lenalidomide-containing regimens.

    Science.gov (United States)

    Sanchez, Larysa; Vesole, David H; Richter, Joshua R; Biran, Noa; Bilotti, Elizabeth; McBride, Laura; Anand, Palka; Ivanovski, Kristin; Siegel, David S

    2017-02-01

    Clinical trials of vorinostat, a Class I/II histone deacetylase inhibitor, in combination with proteasome inhibitors and immunomodulatory agents have shown activity in relapsed/refractory multiple myeloma. This phase IIb, open-label, single-institution study evaluated the efficacy of vorinostat in combination with lenalidomide and dexamethasone in lenalidomide-refractory patients. Patients were considered lenalidomide-refractory if they had no clinical response (vorinostat 400 mg days 1-7 and 15-21, lenalidomide 25 mg days 1-21, and dexamethasone 40 mg days 1, 8, 15 and 22 in 28-day cycles. Twenty-five patients were enrolled, median age was 65 years and patients had received a median of 5 prior regimens. The overall response rate was 24% (6 partial responses) and clinical benefit rate (≥stable disease) was 80%. Median time to a partial response was 1·9 months and median duration of response was 3·3 months. Median progression-free survival was 5·3 months. Most common grade 3/4 adverse events were neutropenia (48%), thrombocytopenia (32%), anaemia (20%) and gastrointestinal toxicities (16%). In this heavily pre-treated population, vorinostat in combination with lenalidomide and dexamethasone was active in lenalidomide-refractory patients. © 2016 John Wiley & Sons Ltd.

  16. Combined modality therapy versus chemotherapy alone as an induction regimen for primary central nervous system lymphoma: a decision analysis.

    Science.gov (United States)

    Prica, Anca; Chan, Kelvin; Cheung, Matthew C

    2012-09-01

    In immunocompetent patients with primary central nervous system (CNS) lymphoma, combined modality therapy (CMT) using high-dose methotrexate and whole brain radiotherapy has improved response rates compared to chemotherapy alone. The trade-off is delayed and potentially devastating treatment-related neurotoxicity. A Markov decision-analytic model compared CMT to chemotherapy alone in patients with primary CNS lymphoma. Baseline probabilities were derived from a systematic literature review. Outcomes were life expectancy and quality-adjusted life expectancy. Sensitivity analyses were performed. The life expectancy was 2·69 years for CMT and 2·77 years for chemotherapy alone. The quality-adjusted life expectancies for the two strategies were 1·70 and 1·67 quality-adjusted life years (QALYs) respectively. In younger patients <60 years of age, CMT yielded a quality-adjusted life expectancy of 2·71 QALYs, compared to 2·09 QALYs for chemotherapy alone, yielding an expected benefit with CMT of 0·62 QALYs or 7·4 quality-adjusted months. There was no difference between the strategies in the older group. The model was robust to key variables for the younger group. The preferred induction strategy for younger patients appears to be CMT, maximizing life expectancy, and QALYs. This analysis confirms that the preferred strategy for older patients is chemotherapy alone. © 2012 Blackwell Publishing Ltd.

  17. Combined effects of functionally-oriented exercise regimens and nutritional supplementation on both the institutionalised and free-living frail elderly (double-blind, randomised clinical trial).

    Science.gov (United States)

    Zak, Marek; Swine, Christian; Grodzicki, Tomasz

    2009-01-28

    Consistently swelling proportion of the frail elderly within a modern society challenges the overstrained public health sector to provide both adequate medical care and comprehensive assistance in their multiple functional deficits of daily living. Easy-to-apply and task-specific ways of addressing this issue are being sought out, with a view to proposing systemic solutions for nationwide application. The present randomised, double-blind, placebo-controlled, 7-week clinical trial aimed to determine whether specifically structured, intensive exercise regimens, combined with nutritional supplementation, might improve and help sustain individual muscle strength and mobility, and possibly enhance individual functional capabilities in an on-going quest for active prevention of care-dependency. Ninety-one frail elderly (F 71 M 20; mean age 79 years) were recruited from both nursing home residents and community dwellers and randomly split into four groups: Group I - progressive resistance exercises (PRE) + functionally-oriented exercises (FOE) + nutritional supplementation (NS), Group II - PRE + FOE + placebo, Group III--standard exercises (SE) + FOE + NS, Group IV - SE + FOE + placebo. Each group pursued a 45 min. exercise session 5 times weekly. The subjects' strength with regard to four muscle groups, i.e. hip and knee extensors and flexons, was assessed at 80% (1 RM) weekly, whereas their balance and mobility at baseline and at the end of the study. The study was completed by 80 subjects. Despite its relatively short duration significant differences in muscle strength were noted both in Group I and Group II (p = 0.01; p = 0.04; respectively), although this did not translate directly into perceptible improvement in individual mobility. Notable improvements in individual mobility were reported in Group III and Group IV (p = 0.002), although without positive impact on individual muscle strength. Comprehensively structured, high-intensity regimen made up of diverse

  18. Combined effects of functionally-oriented exercise regimens and nutritional supplementation on both the institutionalised and free-living frail elderly (double-blind, randomised clinical trial

    Directory of Open Access Journals (Sweden)

    Grodzicki Tomasz

    2009-01-01

    Full Text Available Abstract Background Consistently swelling proportion of the frail elderly within a modern society challenges the overstrained public health sector to provide both adequate medical care and comprehensive assistance in their multiple functional deficits of daily living. Easy-to-apply and task-specific ways of addressing this issue are being sought out, with a view to proposing systemic solutions for nationwide application. Methods The present randomised, double-blind, placebo-controlled, 7-week clinical trial aimed to determine whether specifically structured, intensive exercise regimens, combined with nutritional supplementation, might improve and help sustain individual muscle strength and mobility, and possibly enhance individual functional capabilities in an on-going quest for active prevention of care-dependency. Ninety-one frail elderly (F 71 M 20; mean age 79 years were recruited from both nursing home residents and community dwellers and randomly split into four groups: Group I – progressive resistance exercises (PRE + functionally-oriented exercises (FOE + nutritional supplementation (NS, Group II – PRE + FOE + placebo, Group III – standard exercises (SE + FOE + NS, Group IV – SE + FOE + placebo. Each group pursued a 45 min. exercise session 5 times weekly. The subjects' strength with regard to four muscle groups, i.e. hip and knee extensors and flexons, was assessed at 80% (1 RM weekly, whereas their balance and mobility at baseline and at the end of the study. Results The study was completed by 80 subjects. Despite its relatively short duration significant differences in muscle strength were noted both in Group I and Group II (p = 0.01; p = 0.04; respectively, although this did not translate directly into perceptible improvement in individual mobility. Notable improvements in individual mobility were reported in Group III and Group IV (p = 0.002, although without positive impact on individual muscle strength. Conclusion

  19. Phase 1b study of safety, tolerability and efficacy of R1507, a monoclonal antibody to IGF-1R in combination with multiple standard oncology regimens in patients with advanced solid malignancies.

    Science.gov (United States)

    Mahadevan, Daruka; Sutton, Gregory Ryan; Arteta-Bulos, Rafael; Bowden, Chris J; Miller, Paul J E; Swart, Rachel Elizabeth; Walker, Mark S; Haluska, Paul; Munster, Pamela N; Marshall, John; Hamid, Omid; Kurzrock, Razelle

    2014-03-01

    R1507 is a human IgG1 Mab that binds to the insulin-like growth factor-1 receptor (IGF-1R) and inhibits IGF-1- or IGF-2-mediated anchorage-independent growth of malignant cells. A phase 1b study evaluated the safety, tolerability and efficacy of R1507 in combination with multiple standard oncology regimens. R1507 (3, 5, 9, 10 and 16 mg/kg IV, Q2 W or Q3 W) was added to six treatment regimens: gemcitabine + erlotinib (GE); paclitaxel + bevacizumab (PB); carboplatin + etoposide (CE); mFOLFOX6 + bevacizumab (FB); capecitabine + trastuzumab (CT); and sorafenib (S). If tolerable, R1507 dose was escalated utilizing a 3 + 3 + 6 and a 3 + 9 design. A total of 104 patients enrolled into regimens 1-6: 93 % were non-recent diagnoses. Eighteen withdrew for safety [one death, 17 adverse events (AEs)]. A total of 1,337 AEs any grade, across regimens and doses were nausea, vomiting and diarrhea. A total of 123 had grade ≥3 AEs (n = 28 dose level 1; n = 95 dose level 1) and in 60 patients were myelosuppression, fatigue and mucosal inflammation. ORR (PR plus SD) of evaluable patients across six regimens was 36 % with five PRs: regimens PB (non-small cell lung cancer, nasopharyngeal cancer), CE (melanoma), FB (colon cancer) and S (GIST). The GIST pt (>4 prior therapies) had a PR for 3 years. Three patients (breast cancer, melanoma and adenoid cystic carcinoma) were on study for >1 year; 76 % of patients had SD or better for 4 months. R1507 added to six standard oncology regimens was well tolerated with an ORR of 36 %.

  20. 18-month effectiveness of short-course antiretroviral regimens combined with alternatives to breastfeeding to prevent HIV mother-to-child transmission.

    Directory of Open Access Journals (Sweden)

    Valériane Leroy

    Full Text Available OBJECTIVE: We assessed the 18-month effectiveness of short-course (sc antiretroviral peripartum regimens combined with alternatives to prolonged breastfeeding to prevent mother-to-child transmission (MTCT of HIV-1 in Abidjan, Côte d'Ivoire. METHODOLOGY: HIV-1 infected pregnant women received from >/=32-36 weeks of gestation scZidovudine (ZDV+/-Lamivudine (3TC+single-dose Nevirapine (sdNVP at delivery within the ANRS 1201/1202 DITRAME-Plus cohort (2001-2003. Neonates received a sdNVP+7-day ZDV prophylaxis. Two infant-feeding interventions were systematically offered free of charge: formula-feeding or exclusive shortened breastfeeding with early cessation from four months. The reference group was the ANRS 049a DITRAME cohort (1994-2000 exposed to scZDV from 36 weeks, then to prolonged breastfeeding. Pediatric HIV infection was defined by a positive plasma HIV-1 RNA at any age, or if aged >/=18 months, a positive HIV-1 serology. Turnbull estimates of cumulative transmission risks (CTR and effectiveness (HIV-free survival were compared by exposure group using a Cox model. FINDINGS: Among 926 live-born children enrolled, 107 (11.6% were HIV-infected at 18 months. CTRs were 22.3% (95% confidence interval[CI]:16-30% in the 238 ZDV long-term breastfed reference group, 15.9% (CI:10-27% in the 169 ZDV+sdNVP shortened breastfed group; 9.4% (CI:6-14% in the 195 ZDV+sdNVP formula-fed group; 6.8% (CI:4-11% in the 198 ZDV+3TC+sdNVP shortened breastfed group, and 5.6% (CI:2-10% in the 126 ZDV+3TC+sdNVP formula-fed group. Each combination had a significantly higher effectiveness than the ZDV long-term breastfed group except for ZDV+sdNVP shortened breastfed children, ranging from 51% (CI:20-70% for ZDV+sdNVP formula fed children to 63% (CI:40-80% for ZDV+3TC+NVPsd shortened breastfed children, after adjustment for maternal eligibility for antiretroviral therapy (ART, home delivery and low birth-weight. Substantial MTCT risk reductions are reachable in Africa

  1. Triple Drug Combination of Zidovudine, Efavirenz and Lamivudine Loaded Lactoferrin Nanoparticles: an Effective Nano First-Line Regimen for HIV Therapy.

    Science.gov (United States)

    Kumar, Prashant; Lakshmi, Yeruva Samrajya; Kondapi, Anand K

    2017-02-01

    To enhance efficacy, bioavailability and reduce toxicity of first-line highly active anti-retroviral regimen, zidovudine + efavirenz + lamivudine loaded lactoferrin nanoparticles were prepared (FLART-NP) and characterized for physicochemical properties, bioactivity and pharmacokinetic profile. Nanoparticles were prepared using sol-oil protocol and characterized using different sources such as FE-SEM, AFM, NanoSight, and FT-IR. In-vitro and in-vivo studies have been done to access the encapsulation-efficiency, cellular localization, release kinetics, safety analysis, biodistribution and pharmacokinetics. FLART-NP with a mean diameter of 67 nm (FE-SEM) and an encapsulation efficiency of >58% for each drug were prepared. In-vitro studies suggest that FLART-NP deliver the maximum of its payload at pH5 with a minimum burst release throughout the study period with negligible toxicity to the erythrocytes plus improved in-vitro anti-HIV activity. FLART-NP has improved the in-vivo pharmacokinetics (PK) profiles over the free drugs; an average of >4fold increase in AUC and AUMC, 30% increase in the C max , >2fold in the half-life of each drug. Biodistribution data suggest that FLART-NP has improved the bioavailability of all drugs with less tissue-related inflammation as suggested with histopathological evaluation CONCLUSIONS: The triple-drug loaded nanoparticles have various advantages against soluble (free) drug combination in terms of enhanced bioavailability, improved PK profile and diminished drug-associated toxicity.

  2. A SURVEY ON TREATMENT REGIMENS USED IN THE COMMUNITY AND A TEACHING HOSPITAL FOR OSTEOPOROSIS- A COMBINED STUDY IN NORTHERN KERALA

    Directory of Open Access Journals (Sweden)

    Kunhi Kannan

    2017-03-01

    Full Text Available BACKGROUND Osteoporosis is a common clinical condition with features of low bone mass and microarchitectural collapse of bone tissue with enhanced bone fragility and increased susceptibility to fracture. Nowadays, it is recognised as a major health problem as it leads to an increased risk of developing spontaneous and traumatic fractures. In India, osteoporotic fractures occur more commonly in both sexes and may occur at a younger age than in the western countries. Though exact prevalence of the disease is not available, nearly 36 million Indians maybe suffering from osteoporosis by 2013. At present, most drugs available in the markets decrease bone loss by inhibiting bone resorption, but the upcoming therapies may increase bone mass by directly increasing bone mass as is the case of parathyroid hormone. The aim of the study is to conduct a clinical survey of treatment regimens used in the community and a tertiary hospital for osteoporosis. MATERIALS AND METHODS The clinical and prescription data of 276 patients were analysed in the northern part of Kerala. The diagnostic criteria used for confirmation of osteoporosis, treatment regimens used, their efficacy and side effects were observed and analysed using standard statistical methods. Patients were divided into 2 groups; group A with 116 patients attending the teaching hospital and 160 groups B patients’ information obtained from physicians in the community. RESULTS Among 276 patients, 197 were females and 79 were males with a male-to-female ratio of 1:2.49. Group A showed 28.4% in the 66 to 70 years age group; group B showed 28.75% in the 66 to 70 years age group. The baseline lab investigations were normal. The DXA results in both groups showed T score <2.5 and more in 199 patients (72.10%. The overall incidence of osteoporotic fractures was observed in 63 patients (22.82%. The frequently used treatment regimen was vitamin D and calcium. CONCLUSION Osteoporosis was noted more commonly in

  3. Recombinant interferon alfa-2b combined with a regimen containing doxorubicin in patients with advanced follicular lymphoma. Groupe d'Etude des Lymphomes de l'Adulte.

    Science.gov (United States)

    Solal-Celigny, P; Lepage, E; Brousse, N; Reyes, F; Haioun, C; Leporrier, M; Peuchmaur, M; Bosly, A; Parlier, Y; Brice, P

    1993-11-25

    Interferon alfa and cytotoxic drugs have synergistic effects in patients with non-Hodgkin's lymphoma. In 1986, we designed a clinical trial to evaluate the benefit of concomitant administration of recombinant interferon alfa with a regimen containing doxorubicin in patients with follicular non-Hodgkin's lymphoma. The trial involved 242 patients with advanced low-grade follicular non-Hodgkin's lymphoma selected on the basis of clinical, radiographic, and biologic criteria. All patients were treated with a regimen consisting of cyclophosphamide, doxorubicin, teniposide, and prednisone (CHVP), given monthly for six cycles and then every two months for one year. After randomization, 123 patients also received interferon alfa-2b at a dosage of 5 million units three times weekly for 18 months. The remaining 119 patients received chemotherapy alone. As compared with the patients treated with CHVP only, the patients treated with CHVP plus interferon alfa had a higher overall rate of response (85 percent vs. 69 percent, P = 0.006), a longer median event-free survival (34 months vs. 19 months, P < 0.001), and a higher rate of survival at 3 years (86 percent vs. 69 percent, P = 0.02). Granulocyte toxicity was greater in the patients treated with CHVP plus interferon alfa than in those treated with CHVP alone. There were no treatment-related deaths. Interferon alfa had to be stopped because of toxic effects (fatigue and hepatitis) in 13 patients (11 percent). The addition of interferon alfa to a regimen containing doxorubicin increased the rate of response, event-free survival, and overall survival in patients with advanced follicular non-Hodgkin's lymphoma, without serious toxicity, although some patients were unable to tolerate the side effects.

  4. [Combination of busulfan with increased-dose of fludarabine as conditioning regimen for MDS and MDS-AML patients with allo-HSCT].

    Science.gov (United States)

    Yuan, Jing; Ren, Hanyun; Qiu, Zhixiang; Li, Yuan; Wang, Mangju; Liu, Wei; Xu, Weilin; Sun, Yuhua; Wang, Lihong; Liang, Zeyin; Dong, Yujun; Ou, Jinping; Wang, Wensheng; Yin, Yue; Cen, Xinan; Wang, Qian

    2015-06-01

    To investigate the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS) and secondary acute myelogenous leukemia (MDS-AML) using conditioning regimen with busulfan (Bu) and increased-dose of fludarabine (ID-Flu). A total of 49 patients with MDS or MDS-AML were treated by allo-HSCT, the clinical data was analyzed retrospectively. All patients achieved hematopoietic reconstitution. Neutrophil engraftment was at 10 - 22 days (median 13 days), and platelet engraftment was at 8 - 66 days (median 16 days). The cumulative incidences of Ⅱ-Ⅳ degree acute graft-versus-host disease (GVHD), hemorrhagic cystitis (HC), and hepatic venous occlusive disease (VOD) were 28.6%, 14.3% and 2.0%, respectively. The transplant-related mortality (TRM) was only 4.1% at 100d and 8.2% at 1-92 months of followed-up (median 14 months) period. Overall survival (OS) and disease free survival (DFS) was 75.5%, 73.5%, respectively. Kaplan-Meier curve showed that 3-year OS and 3-year DFS was (71.1 ± 7.8)%, (66.7 ± 8.3)%, respectively, with a relapse incidence (RI) 16.3%. OS for MDS and MDS-AML was 81.5% and 68.2%, and RI in two settings was 3.7%, 31.8%, respectively. OS for MDS-AML at complete remission (CR) and non-CR subgroup was 83.3% and 50.0%, respectively, while cumulative RR was 16.7% and 50.0%, respectively. OS and RI except for non-CR subgroup were 82.1% and 7.7%. Univariate analysis showed that pre-HSCT disease status had correlation with OS (P=0.031), but age, decitabine in conditioning regimen, stem cell source, HLA matching, patient-donor gender, dose of mononuclear cells and GVHD had no correlation with OS. Bu/ID-Flu conditioning regimen for MDS and MDS-AML has high efficiency, fewer complications, lower toxicity and TRM. The OS and DFS were higher and RI was lower except for refractory MDS-AML patients. The regimen is valuable for clinical application.

  5. 5-Fluorouracil combined with the [6S]-stereoisomer of folinic acid in high doses for treatment of patients with advanced colorectal carcinoma. A phase I-II study of two consecutive regimens.

    Science.gov (United States)

    Machover, D; Grison, X; Goldschmidt, E; Zittoun, J; Metzger, G; Richaud, J; Lotz, J P; André, T; Hannoun, L; Marquet, J

    1993-01-01

    Potentiation of the antitumor activity of 5-fluorouracil (5-FU) by folinic acid has been demonstrated in patients with colorectal adenocarcinoma. Modulation is due to the interaction of thymidylate synthase (TS), fluorodeoxyuridylate (FdUMP), and methylene tetrahydrofolate (5,10-CH2-FH4), which leads to the formation of a stable ternary complex with concomitant enzyme inactivation. Folinic acid consists of a mixture of equal parts of two stereoisomers differing in chirality at the C6 carbon of the pteridine ring. Only the levorotatory [6S]-folinic acid is transformed into active folate cofactors. However, the [6R]-stereoisomer is not inert; it was shown to interfere with the [6S] form at the cellular level. The possibility of a deleterious effect of the unnatural stereoisomer on the modulation of 5-FU led us to carry out 2 consecutive phase I-II studies of 5-FU combined with the [6S]-stereoisomer of folinic acid given in high doses for treatment of patients with advanced colorectal carcinoma. Treatment comprised 5-FU by i.v. infusion for 2 hours (the initial dose was 350 mg/m2/d; it was incremented by 25 mg/m2/d until a maximal dose of 550 mg/m2/d) and [6S]-folinic acid (100 mg/m2/d by rapid i.v. injection in Regimen 1, and 100 mg/m2 by rapid i.v. injection followed by a 2-hour infusion of 250 mg/m2 in Regimen 2) for 5 days, every 21 days. Twenty-five pts and 27 pts were assessed in Regimen 1 and in Regimen 2, respectively. They had had no prior chemotherapy. The median follow-up time was 9 months and 15.5 months for patients treated with Regimen 1 and Regimen 2, respectively. For pts treated with Regimen 1, the response rate was 52% (CR, 12%; PR, 40%). The median time to disease progression was 9.2 months. The probability of survival at 12 months was 73%. For pts treated with Regimen 2, the response rate was 37% (CR, 7%; PR, 30%). The median time to disease progression was 8.9 months. The probability of survival at 12 months was 67%. Improvement in quality of life

  6. Classifying insulin regimens

    DEFF Research Database (Denmark)

    Neu, A; Lange, K; Barrett, T

    2015-01-01

    Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1...... diabetes there is little distinctiveness about concepts and the nomenclature is confusing. Even among experts similar terms are used for different strategies. The aim of our review--based on the experiences of the Hvidoere Study Group (HSG)--is to propose comprehensive definitions for current insulin...... variety of insulin regimens applied in each center, respectively. Furthermore, the understanding of insulin regimens has been persistently different between the centers since more than 20 yr. Not even the terms 'conventional' and 'intensified therapy' were used consistently among all members. Besides...

  7. Concurrent split-course chemotherapy and radiotherapy for unresectable stage 3 non-small cell lung cancer: results of a preliminary phase 2 study; Chimioradiotherapie en split course dans les carcinomes bronchiques non a petites cellules de stade 3: resultats preliminaires d'une etude de phase 2

    Energy Technology Data Exchange (ETDEWEB)

    Benchalal, M.; Elgard Maitre, A.M.; Pignol, J.P.; Noirclerc, M.; Prevot, G. [Service d' oncoradiotherapie de Mulhouse, 68 (France); Bourderont, D. [Hopital du Hasenrain, 68 - Mulhouse (France); Salze, P. [Hopital Pasteur, 68 - Colmar (France); Bombaron, P.; Neidhardt, A.C.; Sizaret, O.; Newinger, G.; Zipper, J.M. [Centre Hospitalier de Mulhouse, 68 (France); Lambert, J.; Baumann, J.; Sabountchi, M. [Centre Medical Lalance, 68 - Lutterbach (France)

    1999-12-01

    Purpose: we initiated at Hospital de Mulhouse a prospective phase II study to assess a split-course concurrent radio-chemotherapy in locally advanced non-small cell lung cancer. Materials and methods: from March 1996 to December 1997, 28 patients were included in our study. All patients had a stage III cancer. The chemotherapy scheduled included vinorelbine (20 mg/m{sup 2}/d, d1 and d5), cisplatin (20 mg/m{sup 2}/d, from d1 to d5), and 5-Fluorouracil (350 mg/m{sup 2}/d, from d1 to d5 by continuous infusion). The planned irradiation dose was 12.5 Gy per week with one daily fraction of 2.5 Gy from d1 to d5. Cycles were repeated every four weeks, for four cycles (50 Gy). Patients with a partial or complete response were proposed a fifth cycle. Results: of the 28 patients of the study, only 27 were analysed; one patient had a metastatic disease at diagnosis. Major hematologic toxicity occurred in 26% of the patients. One to five cycles of chemoradiotherapy were administrated per patient (median: four). Four patients had received fewer than three cycles and their responses were not assessable. Of the 23 patients assessed, 12 responses (52%) were observed, three CR (13%) and nine PR (39%). Median follow-up was 14 months, and median survival 13.5 months. One- and two-year survival rates were respectively 63%, and 14%. Local control rates was 11%, and 44% of the patients had a metastatic evolution. Conclusion: very preliminary results of this phase II study are disappointing, and quite inferior to the published results using chemoradiotherapy with conventional or hyperfractionated radiotherapy. Hematologic toxicity is restrictive. This type of chemoradiotherapy cannot be recommended. (author)

  8. In-vivo luminescence model for the study of tumor regression and regrowth following combination regimens with differentiation-promoting agents and photodynamic therapy

    Science.gov (United States)

    Rollakanti, K.; Anand, S.; Maytin, E. V.

    2013-03-01

    Photodynamic therapy with aminolevulinic acid can be modified by pretreatment regimens with drugs such as 5- Fluorouracil (5-FU) or Vitamin D (calcitriol) that enhance accumulation of protoporphyrin IX (PpIX) within tumor tissue which presumably will enhance the therapeutic response to light. However, histological approaches for monitoring therapeutic responses are poorly suited for studying long term survival because large numbers of mice need to be sacrificed. To address this limitation, a non-invasive model to monitor tumor regression and regrowth has been established. Breast cancer cells, stably transfected with firefly luciferase (MDA-Luc cell line), are implanted orthotopically in nude mice (0.25 - 1 x 106 cells/site), and monitored 0-60 min after s.c. injection of luciferin, with Xenogen in-vivo imaging system. Luminescence is detectable at day 1 post-implantation. Tumors are suitable for experimentation on day 6, when daily injections of pretreatment agents (5-FU, 300 mg/kg; calcitriol, 1 μg/kg) begin. On day 9, ALA (75 mg/kg i.p.) is given for 4 hr, followed by illumination (633 nm, 100 J/cm2). Tumor luminescence post- PDT is monitored daily and compared with caliper measurements. Pretreatments (5-FU, calcitriol) by themselves do not inhibit luciferase expression, and all tumors grow at a similar rate during the pretreatment period. Results from in vivo survival experiments can be correlated to survival responses of MDA-Luc cells grown in monolayer cultures +/- PDT and +/- pretreatments, and additional mechanistic information (e.g. Ki67 and E-cadherin expression) obtained. In summary, this noninvasive model will permit testing of the therapeutic survival advantages of various pretreatments during cPDT.

  9. Comparison of a 24-day and a 21-day pill regimen for the novel combined oral contraceptive, nomegestrol acetate and 17β-estradiol (NOMAC/E2): a double-blind, randomized study.

    Science.gov (United States)

    Christin-Maitre, S; Serfaty, D; Chabbert-Buffet, N; Ochsenbein, E; Chassard, D; Thomas, J-L

    2011-06-01

    BACKGROUND Nomegestrol acetate/17β-estradiol (NOMAC/E(2)) is a new monophasic oral contraceptive combining NOMAC (2.5 mg), a highly selective progesterone-derived progestogen, with E(2) (1.5 mg), which is structurally identical to endogenous estrogen. The objective of this study was to compare the effects on ovarian activity of two different NOMAC/E(2) regimens. METHODS This was a double-blind, randomized study. Healthy, premenopausal women (aged 18-38 years, previous menstrual cycle length 28 ± 7 days) were randomized by computer-generated code to once-daily NOMAC/E(2) for three consecutive 28-day cycles: either 24 days with a 4-day placebo interval (n = 40) or 21 days with a 7-day placebo interval (n = 37) per cycle. Follicular growth (primary outcome measure), plasma hormone profiles and bleeding patterns were assessed. RESULTS There was no evidence of ovulation during treatment with either NOMAC/E(2) regimen. The largest follicle diameter was significantly smaller in the 24-day group than in the 21-day group [mean (SD) mm in cycle 2: 9.0 (3.0) versus 11.3 (5.3) (P = 0.02); in cycle 3: 9.2 (3.0) versus 11.5 (6.0) (P = 0.04)]. Mean FSH plasma levels were significantly lower in the 24-day versus the 21-day group on Day 24 of cycles 1 and 2. Withdrawal bleeding duration was significantly shorter in the 24-day than in the 21-day group [mean (SD) days after cycle 1: 3.5 (1.3) versus 5.0 (2.6) (P = 0.002); after cycle 2: 3.9 (1.6) versus 4.8 (1.7) (P = 0.03)]. CONCLUSIONS The 24-day NOMAC/E(2) regimen was associated with greater inhibition of follicular growth and shorter duration of withdrawal bleeding than the 21-day regimen, suggesting the shorter pill-free interval results in a greater margin of contraceptive efficacy and tolerability, and fewer withdrawal symptoms.

  10. Estimated rates of recurrence, cure, and treatment abandonment in patients with pulmonary tuberculosis treated with a -four-drug fixed-dose combination regimen at a tertiary health care facility in the city of Rio de Janeiro, Brazil.

    Science.gov (United States)

    Silva, Vangie Dias da; Mello, Fernanda Carvalho de Queiroz; Figueiredo, Sonia Catarina de Abreu

    2017-01-01

    To estimate the rates of recurrence, cure, and treatment abandonment in patients with pulmonary tuberculosis treated with a four-drug fixed-dose combination (FDC) regimen, as well as to evaluate possible associated factors. This was a retrospective observational study involving 208 patients with a confirmed diagnosis of pulmonary tuberculosis enrolled in the Hospital Tuberculosis Control Program at the Institute for Thoracic Diseases, located in the city of Rio de Janeiro, Brazil. Between January of 2007 and October of 2010, the patients were treated with the rifampin-isoniazid-pyrazinamide (RHZ) regimen, whereas, between November of 2010 and June of 2013, the patients were treated with the rifampin-isoniazid-pyrazinamide-ethambutol FDC (RHZE/FDC) regimen. Data regarding tuberculosis recurrence and mortality in the patients studied were retrieved from the Brazilian Case Registry Database and the Brazilian Mortality Database, respectively. The follow-up period comprised two years after treatment completion. The rates of cure, treatment abandonment, and death were 90.4%, 4.8%, and 4.8%, respectively. There were 7 cases of recurrence during the follow-up period. No significant differences in the recurrence rate were found between the RHZ and RHZE/FDC regimen groups (p = 0.13). We identified no factors associated with the occurrence of recurrence; nor were there any statistically significant differences between the treatment groups regarding adverse effects or rates of cure, treatment abandonment, or death. The adoption of the RHZE/FDC regimen produced no statistically significant differences in the rates of recurrence, cure, or treatment abandonment; nor did it have any effect on the occurrence of adverse effects, in comparison with the use of the RHZ regimen. Estimar as taxas de recidiva, cura e abandono de tratamento em pacientes com tuberculose pulmonar tratados com o esquema de dose fixa combinada (DFC) de quatro drogas e avaliar possíveis fatores associados

  11. Effects of TC regimen combined chemotherapy on serum levels of TSGF, PRL, HE4 and inflammatory factors in patients with endometrial carcinoma

    Directory of Open Access Journals (Sweden)

    Huan-Huan Chen

    2017-05-01

    Full Text Available Objective: To observe the effects of TC chemotherapy on the basis of surgical treatment on Endometrial carcinoma patients’ serum TSGF, PRL, HE4 and TNF-α, CRP, VEGF, IL-8 levels. Methods: 106 cases of endometrial carcinoma in our hospital from September 2014 to September 2016 were retrospectively analyzed and divided into control group and observation group, with 49 patients in the control group,57 patients in the observation group. All patients were given laparoscopic surgery, the patients in the observation group were given on the basis of laparoscopic surgery TC regimen (paclitaxel + carboplatin chemotherapy for 2 courses, fasting venous blood before and after treatment in the morning was taken and centrifuged, and then used ELISA method to detect and compare the serum levels of TSGF, PRL, HE4 and TNF-α, CRP, VEGF, IL-8. Results: (1 Before treatment, there was no statistically significant difference in the serum TSGF, PRL, HE4 levels between the two groups. After treatment, compared with the same group before treatment, the serum TSGF, PRL, HE4 levels of the two groups were significantly lower, and those levels of observation group were significantly better than the control group, there was significant difference between the two groups; (2 Before treatment, there was no statistically significant difference in the serum TNF-α, CRP, VEGF, IL-8 levels between the two groups. After treatment, compared with the same group before treatment, the serum TNF-α, CRP, VEGF, IL-8 levels of the two groups were significantly lower, and those levels of observation group were significantly better than the control group, there was significant difference between the two groups. Conclusion: The treatment of TC chemotherapy on the basis of surgical treatment can significantly improve the patient's serum TSGF, PRL, HE4 and TNF-α, CRP, VEGF, IL-8 levels, it indicated that adjuvant chemotherapy with TC could not only improve the curative effect, control local

  12. Colostrum replacer feeding regimen, addition of sodium bicarbonate, and milk replacer: the combined effects on absorptive efficiency of immunoglobulin G in neonatal calves.

    Science.gov (United States)

    Cabral, R G; Cabral, M A; Chapman, C E; Kent, E J; Haines, D M; Erickson, P S

    2014-01-01

    Eighty Holstein and Holstein cross dairy calves were blocked by birth date and randomly assigned to 1 of 8 treatments within each block to examine the effect of a colostrum replacer (CR) feeding regimen, supplementation of CR with sodium bicarbonate (NaHCO3), and provision of a milk replacer (MR) feeding on IgG absorption. Calves were offered a CR containing 184.5g/L of IgG in either 1 feeding at 0h (within 30 min of birth), with or without 30g of NaHCO3, with or without a feeding of MR at 6h of age, or 2 feedings of CR (123g of IgG at 0h with or without 20g of NaHCO3 and 61.5g of IgG at 6h with or without 10g of NaHCO3), with or without a MR feeding at 12h. Therefore, treatments were (1) 1 feeding of CR; (2) 2 feedings of CR; (3) 1 feeding of CR + 30g of NaHCO3; (4) 2 feedings of CR + 30g of NaHCO3; (5) 1 feeding of CR + MR feeding; (6) 2 feedings of CR + MR feeding; (7) 1 feeding of CR + 30g NaHCO3 + MR feeding; and (8) 2 feedings of CR + 30g NaHCO3 + MR feeding. Blood samples were obtained at 0, 6, 12, 18, and 24h after birth and were analyzed for IgG via radial immunoassay. Results indicated that CR feeding schedule, MR feeding, and the interactions CR × Na, CR × MR, and CR × Na × MR were similar for 24-h serum IgG, apparent efficiency of absorption, or area under the curve. Serum IgG at 24h, apparent efficiency of absorption, and area under the curve were decreased with addition of NaHCO3 compared with calves not supplemented with NaHCO3. These data indicate that supplementation of CR with NaHCO3 is not beneficial to IgG absorption and feeding MR within 6h of CR feeding does not affect IgG absorption. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  13. Safety and High Level Efficacy of the Combination Malaria Vaccine Regimen of RTS,S/AS01B With Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara Vectored Vaccines Expressing ME-TRAP.

    Science.gov (United States)

    Rampling, Tommy; Ewer, Katie J; Bowyer, Georgina; Bliss, Carly M; Edwards, Nick J; Wright, Danny; Payne, Ruth O; Venkatraman, Navin; de Barra, Eoghan; Snudden, Claudia M; Poulton, Ian D; de Graaf, Hans; Sukhtankar, Priya; Roberts, Rachel; Ivinson, Karen; Weltzin, Rich; Rajkumar, Bebi-Yassin; Wille-Reece, Ulrike; Lee, Cynthia K; Ockenhouse, Christian F; Sinden, Robert E; Gerry, Stephen; Lawrie, Alison M; Vekemans, Johan; Morelle, Danielle; Lievens, Marc; Ballou, Ripley W; Cooke, Graham S; Faust, Saul N; Gilbert, Sarah; Hill, Adrian V S

    2016-09-01

    The need for a highly efficacious vaccine against Plasmodium falciparum remains pressing. In this controlled human malaria infection (CHMI) study, we assessed the safety, efficacy and immunogenicity of a schedule combining 2 distinct vaccine types in a staggered immunization regimen: one inducing high-titer antibodies to circumsporozoite protein (RTS,S/AS01B) and the other inducing potent T-cell responses to thrombospondin-related adhesion protein (TRAP) by using a viral vector. Thirty-seven healthy malaria-naive adults were vaccinated with either a chimpanzee adenovirus 63 and modified vaccinia virus Ankara-vectored vaccine expressing a multiepitope string fused to TRAP and 3 doses of RTS,S/AS01B (group 1; n = 20) or 3 doses of RTS,S/AS01B alone (group 2; n = 17). CHMI was delivered by mosquito bites to 33 vaccinated subjects at week 12 after the first vaccination and to 6 unvaccinated controls. No suspected unexpected serious adverse reactions or severe adverse events related to vaccination were reported. Protective vaccine efficacy was observed in 14 of 17 subjects (82.4%) in group 1 and 12 of 16 subjects (75%) in group 2. All control subjects received a diagnosis of blood-stage malaria parasite infection. Both vaccination regimens were immunogenic. Fourteen protected subjects underwent repeat CHMI 6 months after initial CHMI; 7 of 8 (87.5%) in group 1 and 5 of 6 (83.3%) in group 2 remained protected. The high level of sterile efficacy observed in this trial is encouraging for further evaluation of combination approaches using these vaccine types. NCT01883609. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  14. Neglected Tropical Diseases: Treatment of Dermatological Manifestation of Filariasis with Combination Regimen of Albendazole, Ivermectin, and Loratadine: A Case Report from a Suburban Community in Nigeria

    Directory of Open Access Journals (Sweden)

    Osede Ignis Iribhogbe

    2017-06-01

    Full Text Available Threadlike filarial nematodes have been identified as the causative agent of filariasis. Cutaneous filariasis is caused primarily by Loa loa, Onchocerca volvulus, and Mansonella streptocerca. These parasites occupy the subcutaneous layer of the skin. However, other filarial parasites are usually associated with varying degrees of dermatological manifestations. In the present discourse, two cases of cutaneous filariasis were diagnosed in two female patients (21 and 40 years old, respectively in Remitch Clinic and Maternity located in a nonriverine community in Ekpoma, Edo State, Nigeria. In this report, patients with body mass index (BMI of 18.97 and 23.45 kg/m2, respectively, presented on two different occasions at least 6 months apart with hyperpigmented skin lesions in the upper and lower limbs, respectively. There was associated intense pruritus with no evidence of lymphadenopathy and lymphoedema. Following laboratory confirmation of filariasis, the patients were placed on a single oral dose combination of albendazole (400 mg + ivermectin (200 mcg/kg, while oral doses of loratadine 10 mg were administered daily for 5 days. Patients were carefully followed up for 6 weeks during which recession of the lesion and untoward reactions were monitored. It was observed that within 6 weeks of treatment, there was a dramatic recession of skin lesion. Adverse effect reported from use of the combination was mild. This case report revealed that cutaneous filariasis is not an uncommon presentation of filariasis infestation in Nigeria. The report also validates the safety and efficacy of the combination in the management of cutaneous manifestation of the disease.

  15. Long-term follow-up of the effects of fecal microbiota transplantation in combination with soluble dietary fiber as a therapeutic regimen in slow transit constipation.

    Science.gov (United States)

    Zhang, Xueying; Tian, Hongliang; Gu, Lili; Nie, Yongzhan; Ding, Chao; Ge, Xiaolong; Yang, Bo; Gong, Jianfeng; Li, Ning

    2018-02-06

    As some studies have reported that strategies targeting the gut microbiota such as fecal microbiota transplantation (FMT) with or without other microecological therapy might have efficacy in treating slow transit constipation (STC), we conducted a single-center, open-label trial to study the long-term effect of FMT combined with soluble dietary fiber (pectin) on STC. Thirty-one adult patients with STC were enrolled into the trial. Patients received 6-day FMT procedures repeatedly for the first 3 months and soluble dietary fiber (pectin) daily during the follow-up. The rate of clinical remission and improvement, stool consistency, the Wexner constipation scale, and assessment of constipation-related symptoms were evaluated at week 4 and 1 year later. The clinical remission and improvement rates at week 4 were 69.0% (20/29) and 75.9% (22/29), respectively. At the end of the study, 48.3% (14/29) of patients continued to have at least three complete spontaneous bowel movements per week and 58.6% (17/29) of patients showed clinical improvements. Stool consistency, the Wexner constipation scale, and constipation symptoms improved both at short-term and long-term follow-up. The results indicated that FMT in combination with soluble dietary fiber (pectin) had both short-term and long-term efficacy in treating STC.

  16. Radioprotective efficacy of dipyridamole and AMP combination in fractionated radiation regimen, and its dependence on the time of administration of the drugs prior to irradiation

    International Nuclear Information System (INIS)

    Hofer, M.; Pospisil, M.; Netikova, J.; Hola, J.; Znojil, V.; Vacha, J.

    1995-01-01

    The authors have recently demonstrated that a combined administration of dipyridamole and adenosine monophosphate to mice induces radioprotective effects in terms of postirradiation hematopoietic recovery in animals irradiated with a single dose. The aim of the present experiments was to investigate the radioprotective ability of the drug combination under conditions of fractionated radiation. It was shown that administration of the drugs either 15 or 60 min before each of the five daily 3-Gy doses of gamma radiation enhances hematopoietic recovery and survival of mice exposed to an additional 'top-up' dose of 3.5 Gy. Furthermore, it was ascertained that administration of the drugs 60 min prior to irradiation is more effective than administration of the drugs 15 min prior to irradiation. Due to the evidence that administration of the drugs 15 min prior to irradiation protects the organism mainly via mechanisms of systemic hypoxia while the pretreatment 60 min before irradiation avoids the role of hypoxia and mainly induces cell proliferation effects, the present results suggest a more protective role of mechanisms stimulating hematopoiesis under conditions of fractionated radiation. The data may provide a basis for more rational use of radioprotection in fractionated radiation techniques. (author) 1 tab., 1 fig., 25 refs

  17. The Association of Combined GSTM1 and CYP2C9 Genotype Status with the Occurrence of Hemorrhagic Cystitis in Pediatric Patients Receiving Myeloablative Conditioning Regimen Prior to Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Chakradhara Rao S. Uppugunduri

    2017-07-01

    Full Text Available Hemorrhagic cystitis (HC is one of the complications of busulfan-cyclophosphamide (BU-CY conditioning regimen during allogeneic hematopoietic stem cell transplantation (HSCT in children. Identifying children at high risk of developing HC in a HSCT setting could facilitate the evaluation and implementation of effective prophylactic measures. In this retrospective analysis genotyping of selected candidate gene variants was performed in 72 children and plasma Sulfolane (Su, water soluble metabolite of BU levels were measured in 39 children following treatment with BU-CY regimen. The cytotoxic effects of Su and acrolein (Ac, water soluble metabolite of CY were tested on human urothelial cells (HUCs. The effect of Su was also tested on cytochrome P 450 (CYP function in HepaRG hepatic cells. Cumulative incidences of HC before day 30 post HSCT were estimated using Kaplan–Meier curves and log-rank test was used to compare the difference between groups in a univariate analysis. Multivariate Cox regression was used to estimate hazard ratios with 95% confidence intervals (CIs. Multivariate analysis included co-variables that were significantly associated with HC in a univariate analysis. Cumulative incidence of HC was 15.3%. In the univariate analysis, HC incidence was significantly (p < 0.05 higher in children older than 10 years (28.6 vs. 6.8% or in children with higher Su levels (>40 vs. <11% or in carriers of both functional GSTM1 and CYP2C9 (33.3 vs. 6.3% compared to the other group. In a multivariate analysis, combined GSTM1 and CYP2C9 genotype status was associated with HC occurrence with a hazards ratio of 4.8 (95% CI: 1.3–18.4; p = 0.02. Ac was found to be toxic to HUC cells at lower concentrations (33 μM, Su was not toxic to HUC cells at concentrations below 1 mM and did not affect CYP function in HepaRG cells. Our observations suggest that pre-emptive genotyping of CYP2C9 and GSTM1 may aid in selection of more effective prophylaxis to

  18. Efficacy benefit of an NK1 receptor antagonist (NK1RA) in patients receiving carboplatin: supportive evidence with NEPA (a fixed combination of the NK1 RA, netupitant, and palonosetron) and aprepitant regimens.

    Science.gov (United States)

    Jordan, Karin; Gralla, Richard; Rizzi, Giada; Kashef, Kimia

    2016-11-01

    Antiemetic guideline recommendations are inconsistent as to whether a neurokinin-1 receptor antagonist (NK1 RA) should be administered with a 5-hydroxytryptamine-3 (5HT3) RA + dexamethasone (DEX) in patients receiving carboplatin. Patients receiving cisplatin routinely receive an NK1 RA-containing regimen with a resulting 14-22 % benefit in no emesis rates over a 5-HT3 RA/DEX control. Recent studies suggest a similar benefit in patients receiving carboplatin. NEPA is the first fixed antiemetic combination agent and comprises the highly selective NK1 RA, netupitant, and pharmacologically distinct 5-HT3 RA, palonosetron (PALO). This paper presents the efficacy of NEPA in the subset of patients receiving carboplatin in a phase 3 trial (NCT01376297), in the context of aprepitant (APR) data in the carboplatin setting. One hundred ninety-six patients (47 % of all study patients: n = 145 NEPA + DEX; n = 51 APR + PALO + DEX) received carboplatin in a multinational, double-blind, randomized phase 3 study. Complete response (CR: no emesis/rescue) and no significant nausea (NSN: score ≤25 on 100 mm visual analog scale) rates were calculated. Cycle 1-4 overall (0-120 h) CR rates were similar for NEPA (80, 91, 92, and 93 %) and APR (82, 88, 88, and 90 %). Overall NSN rates were also similar (NEPA 84-96 %; APR 82-90 %). Response rates for NEPA and APR regimens were similar and consistent with prior studies evaluating the contribution of adding NK1 RAs in patients receiving carboplatin. Considering such evidence, guideline groups/practitioners should consider giving a NK1 RA antiemetic triplet in patients receiving carboplatin.

  19. Combined modality therapy versus chemotherapy alone as an induction regimen for primary central nervous system lymphoma: a cost-effectiveness analysis.

    Science.gov (United States)

    Prica, A; Chan, K; Cheung, M

    2014-10-01

    In immunocompetent patients with primary central nervous system lymphoma (PCNSL), combined modality therapy (CMT) using high-dose methotrexate and radiotherapy (WBRT) has improved response rates compared with chemotherapy alone. The trade-off is delayed and potentially devastating treatment-related neurotoxicity (NT). A cost-effectiveness analysis using a Markov model compared CMT with chemotherapy alone in age-stratified patients with PCNSL. Baseline probabilities were derived from a systematic literature review. Direct and lost productivity costs were collected from a Canadian perspective and presented in Can$ in 2011. Outcomes were life expectancy, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio. The quality-adjusted life expectancy was 1.55 QALYs for CMT and 1.53 QALYs for chemotherapy alone. In younger patients (aged <60 years), CMT yielded 2.44 QALYs, compared with 1.89 QALYs for chemotherapy alone, yielding an expected benefit with CMT of 0.55 QALYs or 6.6 quality-adjusted months. The CMT strategy dominated in younger patients, as it was Can$11 951 less expensive than chemotherapy alone. The chemotherapy-alone strategy dominated in older patients, as it was Can$11 244 less expensive than CMT, and there was no difference in QALYs between the strategies. The model was robust in sensitivity analyses of key variables tested through the plausible ranges obtained from costing sources and published literature. The preferred induction strategy for younger patients with PCNSL appears to be CMT, which minimized cost while maximizing life expectancy and QALYs. This analysis confirms that the preferred strategy for older patients is chemotherapy alone. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Comparing a combination of penicillin G and gentamicin to a combination of clindamycin and amikacin as prophylactic antibiotic regimens in prevention of clean contaminated wound infections in cancer surgery

    International Nuclear Information System (INIS)

    El-Mahallawy, H.A.; Hassan, S.Sh.; Khalifa, H.I.; Safa, M.M.E.; Khafagy, M.M.

    2013-01-01

    Background and aim: Appropriate antibiotic selection and timing of administration for prophylaxis are crucial to reduce the likelihood of surgical site infection (SSI) after a clean contaminated cancer surgery. Our aim is to compare the use of two prophylactic antibiotic (PA) regimens as regards efficacy, timing, and cost. Patients and methods: Two hundred patients with gastric, bladder, or colorectal cancer were randomized to receive preoperative PA, group A received penicillin G sodium and gentamicin and group B received clindamycin and amikacin intravenously. The demographic data of patients were collected, and they were observed for wound infections. Results: Infected wounds occurred in 19 patients with a rate of 9.5%. Highest incidence of SSI was among bladder cancer patients (14.2%); p = 0.044. The rate of SSI was 11 % in group A, and 8% in group B, p = 0.469. The cost of PA administered in group A was significantly less than that of group B (21.96 ± 3.22 LE versus 117.05 ± 12.74 LE, respectively; p < 0.001). SSI tended to be higher among those who had longer time for antibiotic and incision (≥ 30 min) than those who had shorter time interval (<30 min), (13% vs. 6.5%, respectively). Conclusion: Both penicillin + gentamicin and clindamycin + amikacin are safe and effective for the prevention of SSI in clean contaminated operative procedures. In a resource limited hospital, a regimen including penicillin + gentamicin is a cost-effective alternative for the more expensive and broader coverage of clindamycin + amikacin. Timing of PA is effective in preventing SSIs when administered 30 min before the start of surgery

  1. Effects of Combined CCR5/Integrase Inhibitors-Based Regimen on Mucosal Immunity in HIV-Infected Patients Naïve to Antiretroviral Therapy: A Pilot Randomized Trial.

    Directory of Open Access Journals (Sweden)

    Sergio Serrano-Villar

    2016-01-01

    Full Text Available Whether initiation of antiretroviral therapy (ART regimens aimed at achieving greater concentrations within gut associated lymphoid tissue (GALT impacts the level of mucosal immune reconstitution, inflammatory markers and the viral reservoir remains unknown. We included 12 HIV- controls and 32 ART-naïve HIV patients who were randomized to efavirenz, maraviroc or maraviroc+raltegravir, each with fixed-dose tenofovir disoproxil fumarate/emtricitabine. Rectal and duodenal biopsies were obtained at baseline and at 9 months of ART. We performed a comprehensive assay of T-cell subsets by flow cytometry, T-cell density in intestinal biopsies, plasma and tissue concentrations of antiretroviral drugs by high-performance liquid chromatography/mass spectroscopy, and plasma interleukin-6 (IL-6, lipoteichoic acid (LTA, soluble CD14 (sCD14 and zonulin-1 each measured by ELISA. Total cell-associated HIV DNA was measured in PBMC and rectal and duodenal mononuclear cells. Twenty-six HIV-infected patients completed the follow-up. In the duodenum, the quadruple regimen resulted in greater CD8+ T-cell density decline, greater normalization of mucosal CCR5+CD4+ T-cells and increase of the naïve/memory CD8+ T-cell ratio, and a greater decline of sCD14 levels and duodenal HIV DNA levels (P = 0.004 and P = 0.067, respectively, with no changes in HIV RNA in plasma or tissue. Maraviroc showed the highest drug distribution to the gut tissue, and duodenal concentrations correlated well with other T-cell markers in duodenum, i.e., the CD4/CD8 ratio, %CD4+ and %CD8+ HLA-DR+CD38+ T-cells. Maraviroc use elicited greater activation of the mucosal naïve CD8+ T-cell subset, ameliorated the distribution of the CD8+ T-cell maturational subsets and induced higher improvement of zonulin-1 levels. These data suggest that combined CCR5 and integrase inhibitor based combination therapy in ART treatment naïve patients might more effectively reconstitute duodenal immunity, decrease

  2. Long-term efficacy and safety of a monophasic combined oral contraceptive containing 0.02 mg ethinylestradiol and 2 mg chlormadinone acetate administered in a 24/4-day regimen.

    Science.gov (United States)

    Brucker, Cosima; Hedon, Bernard; The, Hok Sien; Höschen, Kornelia; Binder, Natascha; Christoph, Annette

    2010-06-01

    This study was conducted to assess the long-term efficacy and safety of a low-dose monophasic combined oral contraceptive (COC) containing 0.02 mg ethinylestradiol (EE) and 2 mg chlormadinone acetate (CMA) in a novel regimen administered daily for 24 days followed by a 4-day placebo interval. In this multicenter, uncontrolled, Phase III trial, 1665 subjects took the COC 0.02 mg EE/2 mg CMA for up to 21 cycles. The overall Pearl Index was the primary end point; cycle control, safety, effect on acne and seborrhea, and changes in body weight and libido were secondary end points. Contraceptive efficacy was analyzed for 1653 subjects completing 21,495 cycles. Six pregnancies occurred during trial duration with one attributable to method failure. The overall Pearl Index for the first year of use was 0.33 (95% confidence interval, 0.09-0.85). The mean number of bleeding/spotting days during six 90-day reference periods (RPs) decreased from 17.0 (RP 1) to 11.7 (RP 6), and the number of bleeding episodes per RP decreased from 3.8 (RP 1) to 2.7 (RP 6). Among subjects who presented with acne at the baseline visit, a decrease of papules/pustules and comedones was observed during the course of the trial. The most common "at least possibly related" adverse events were headache, breast discomfort and nausea. The tolerability and well-being was reported as being excellent or good in the majority of trial subjects (84.6% and 80.2%, respectively). The low-dose COC 0.02 mg EE/2 mg CMA administered daily for 24 days followed by a 4-day placebo interval provides high contraceptive efficacy combined with an adequate cycle control and safety profile, beneficial effects on acne, and is well tolerated.

  3. Short-Term Immunogenicity and Safety of an Accelerated Pre-Exposure Prophylaxis Regimen With Japanese Encephalitis Vaccine in Combination With a Rabies Vaccine: A Phase III, Multicenter, Observer-Blind Study.

    Science.gov (United States)

    Jelinek, Tomas; Burchard, Gerd D; Dieckmann, Sebastian; Bühler, Silja; Paulke-Korinek, Maria; Nothdurft, Hans D; Reisinger, Emil; Ahmed, Khaleel; Bosse, Dietrich; Meyer, Seetha; Costantini, Marco; Pellegrini, Michele

    2015-01-01

    The current Japanese encephalitis (JE) vaccination regimen requires two doses and 4 weeks to complete, which may not always be feasible for travelers on short notice. One of the primary endpoints of this phase III study was to demonstrate noninferiority of immune responses to a JE vaccine following an accelerated 1-week JE vaccination regimen administered concomitantly with a rabies vaccine as compared to a standard 4-week JE regimen alone. In addition, the immunogenicity of concomitant administration of JE and rabies vaccines following standard regimens was evaluated, as well as the tolerability and safety profile of each regimen under study. Healthy adults aged 18 to ≤65 years were randomized to regimens with an accelerated or standard schedule: JE+rabies-standard (n = 167), JE+rabies-accelerated (n = 217) or JE-standard (n = 56). Immunogenicity against JE antigen was assessed by a 50% plaque reduction neutralization test (PRNT50 ) titer of ≥1 : 10, measured 28 days after last active vaccine (LAV) administration. Solicited reactions were collected 7 days after each vaccination; spontaneously reported adverse events (AEs) and serious AEs were monitored up to day 57. This paper reports results until day 57. Noninferiority of immune responses was established for JE+rabies-accelerated compared to the JE-standard regimen 28 days after LAV administration. Overall, 99% and 100% of subjects in the JE+rabies-accelerated and JE-standard groups, respectively, achieved PRNT50 titers of ≥1 : 10 at 28 days after LAV administration. No impact of concomitant rabies vaccination was observed either on immune responses or on the safety profile of the JE vaccine. This was the first randomized, controlled trial that demonstrated the strong short-term immunogenicity of a new, accelerated, 1-week JE-regimen, which was noninferior to that of the standard regimen, with a satisfactory tolerability and safety profile and no impact of concomitant rabies vaccination. This accelerated

  4. Pilot study of alternating radiotherapy and three-drug combined chemotherapy consisting of ifosfamide, cisplatin and vindesine in localized inoperable non-small cell lung cancer

    International Nuclear Information System (INIS)

    Rikimaru, Toru; Tanaka, Yasuyuki; Ichikawa, Yoichiro; Oizumi, Kotaro; Fukurono, Kazuyoshi; Hayabuchi, Naofumi

    1993-01-01

    During the period from February 1991 through October 1992, we conducted a pilot phase II trial of an 'Alternating Radiotherapy and Chemotherapy' for 15 patients with localized inoperable non-small cell lung cancer. The combined regimen, consisting of ifosfamide 1.5 g/m 2 on days 1 through 3, cisplatin 80 mg/m 2 and vindesine 3 mg/m 2 on day 1, was given repeatedly every 4 weeks. Patients were treated in a split course fashion with combination chemotherapy sandwiched between radiation therapy (total dose 60 Gy). Of 15 evaluable patients, complete remission, partial remission and no change were obtained in 1, 13 and 1 patients, respectively, with an overall response rate of 93.3%. The median survival for all patients was 62 weeks. Hematologic toxicity was severe and was judged to be dose limiting. It was, however, clinically manageable with colony stimulating factor. These results indicate that this alternating radiotherapy and chemotherapy is feasible for localized non-small cell lung cancer and warrants further clinical trials. (author)

  5. Metronomic chemotherapy regimens in oncology

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2016-01-01

    Full Text Available Metronomic chemotherapy implies the regular use of cytotoxic agents in doses much smaller than the maximum tolerable doses for a long time. Preclinical experiments show that this treatment option has a many-sided (antiangiogenic, immunostimulating, and direct cytotoxic effect on tumor. Moreover, this approach has gained the widest acceptance in treating patients with metastatic breast cancer in clinical practice. By taking into account the high activity of angiogenesis in colon cancer progression, it is interesting to study the impact of metronomic chemotherapy regimens for this nosological entity as well. This literature review considers not only the history of metronomic chemotherapy, the mechanisms of action, and a range of drugs having an antitumor effect in the metronomic regimens, but also analyzes clinical trials of metronomic chemotherapy regimens in patients with metastatic colon cancer.

  6. A comparative study of various therapeutic regimens in urticaria

    Directory of Open Access Journals (Sweden)

    Mukhopadhyay Amiyakumar

    1995-01-01

    Full Text Available 127 patients of urticaria were treated with chlorpheniramine maleate alone and in combination with cyproheptadine hydrochloride, ranitidine and doxepin and levamisole. Chlorpheniramine and doxepin combination showed a satisfactory result in 88.46% of patients. Overall study showed that a combination regimen is better than the antihistaminics alone. Drowsiness was the commonest side effect. Levamisole and chlorpheniramine maleate combination was found to be more effective than the antihimstamine alone.

  7. Intravenous and intramuscular magnesium sulphate regimens in ...

    African Journals Online (AJOL)

    1993-09-03

    Sep 3, 1993 ... parenterally, usually according to one of two popular regimens: the intramuscular (IM) regimen introduced by. Pritchard' and a continuous intravenous (IV) infusion described by Zuspan! Sibai et a/.3 have reported that lower serum magnesium values are achieved with Zuspan's regimen (maintenance dose ...

  8. A Phase 2 Open Label, Single-Arm Trial to Evaluate the Combination of Cetuximab Plus Taxotere, Cisplatin, and 5-Flurouracil as an Induction Regimen in Patients With Unresectable Squamous Cell Carcinoma of the Head and Neck

    Energy Technology Data Exchange (ETDEWEB)

    Mesía, Ricard, E-mail: rmesia@iconcologia.net [Medical Oncology Department, Institut Català d' Oncologia L' Hospitalet, Barcelona (Spain); Vázquez, Silvia [Medical Oncology Department, Institut Català d' Oncologia L' Hospitalet, Barcelona (Spain); Grau, Juan J. [Medical Oncology Department, Hospital Clínic i Provincial, Barcelona (Spain); García-Sáenz, Jose A. [Medical Oncology Department, Hospital Clínico San Carlos, Madrid (Spain); Lozano, Alicia [Radiation Oncology Department, Institut Català d' Oncologia L' Hospitalet, Barcelona (Spain); García, Carlos [Medical Oncology Department, Hospital General Yagüe, Burgos (Spain); Carles, Joan [Medical Oncology Department, Hospital del Mar, Barcelona (Spain); Irigoyen, Antonio [Medical Oncology Department, Hospital Virgen de las Nieves, Granada (Spain); Mañós, Manel [Department of Otorhinolaryngology, Hospital de Bellvitge, Barcelona (Spain); García-Paredes, Beatriz [Medical Oncology Department, Hospital Clínico San Carlos, Madrid (Spain); Barco, Elvira del [Medical Oncology Department, Gregorio Marañón University Hospital, Madrid (Spain); Taberna, Miren [Medical Oncology Department, Institut Català d' Oncologia L' Hospitalet, Barcelona (Spain); Escobar, Yolanda [Medical Oncology Department, Gregorio Marañón University Hospital, Madrid (Spain); and others

    2016-02-01

    Purpose: Despite treatment, prognosis of unresectable squamous cell carcinoma of the head and neck (SCCHC) is dismal. Cetuximab therapy has proven to increase the clinical activity of radiation therapy and chemotherapy in patients with locoregional advanced disease with an acceptable toxicity profile. We designed a phase 2 trial to evaluate the efficacy of docetaxel, cisplatin, and 5-fluorouracil (TPF) plus cetuximab (C-TPF) as an induction regimen in patients with unresectable SCCHN. Methods and Materials: A single-arm phase 2 trial was conducted. Eligible patients included those with untreated unresectable SCCHC, World Health Organization performance status of 0 to 1, 18 to 70 years of age. Treatment consisted of four 21-day cycles of TPF (docetaxel, 75 mg/m{sup 2} day 1; cisplatin, 75 mg/m{sup 2} day 1; 5-fluorouracil [5-FU], 750 mg/m{sup 2} day 1-5) and cetuximab, 250 mg/m{sup 2} weekly (loading dose of 400 mg/m{sup 2}). Prophylactic granulocyte colony-stimulating factor and antibiotic support were given. After induction, sequential accelerated radiation therapy with concomitant boost (69.9 Gy) and weekly cetuximab therapy were delivered in the absence of disease progression. The primary endpoint was objective response rate (ORR) to C-TPF. Results: Fifty patients were enrolled across 8 centers. Median age was 54 years; disease was stage IV; oropharynx and hypopharynx were the most common primary sites. Eighty-two percent received 4 cycles of C-TPF, and 86% started sequential treatment based on radiation therapy and cetuximab. ORR after C-TPF was 86% (95% confidence interval [CI]: 73%-94%) and 24% had complete response (CR). With a median follow-up of 40.7 months, median overall survival (OS) was 40.7 months. The 2-year actuarial locoregional control (LRC) rate was 57%. The most common drug-related grade 3 or 4 toxicities during induction were neutropenia (24%), neutropenic fever (24%), and diarrhea (20%). There were 3 treatment-related deaths (6

  9. Patients' Willingness to Take Multiple-Tablet Antiretroviral Therapy Regimens for Treatment of HIV

    NARCIS (Netherlands)

    Engelhard, Esther A N; Smit, Colette; Vervoort, Sigrid C J M; Smit, Peter J; Nieuwkerk, Pythia T.; Kroon, Frank P; Reiss, Peter; Brinkman, Kees; Geerlings, Suzanne E.

    BACKGROUND: The costs of combination antiretroviral therapy (cART) for HIV, consisting of separate, particularly generic, components (multiple-tablet regimens, MTR) are generally much lower than those of single-tablet regimens (STR) comprising the same active ingredients. OBJECTIVES: To assess

  10. Patients' Willingness to Take Multiple-Tablet Antiretroviral Therapy Regimens for Treatment of HIV

    NARCIS (Netherlands)

    Engelhard, Esther A. N.; Smit, Colette; Vervoort, Sigrid C. J. M.; Smit, Peter J.; Nieuwkerk, Pythia T.; Kroon, Frank P.; Reiss, Peter; Brinkman, Kees; Geerlings, Suzanne E.

    2016-01-01

    The costs of combination antiretroviral therapy (cART) for HIV, consisting of separate, particularly generic, components (multiple-tablet regimens, MTR) are generally much lower than those of single-tablet regimens (STR) comprising the same active ingredients. To assess whether patients would be

  11. Once-daily dose regimen of ribavirin is interchangeable with a twice-daily dose regimen: randomized open clinical trial

    Directory of Open Access Journals (Sweden)

    Balk JM

    2015-08-01

    Full Text Available Jiska M Balk,1 Guido RMM Haenen,1 Özgür M Koc,2 Ron Peters,3 Aalt Bast,1 Wim JF van der Vijgh,1 Ger H Koek,4 1Department of Toxicology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, 2Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, 3DSM Resolve, Geleen, 4Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands Background: The combination of ribavirin (RBV and pegylated interferon (PEG-IFN is effective in the treatment of chronic hepatitis C infection. Reducing the frequency of RBV intake from twice to once a day will improve compliance and opens up the opportunity to combine RBV with new and more specific direct-acting agents in one pill. Therefore, the purpose of this study was to evaluate the pharmacokinetic profile of RBV in a once-daily to twice-daily regimen. The secondary aim was to determine tolerability as well as the severity and differences in side effects of both treatment regimens. Methods: In this randomized open-label crossover study, twelve patients with chronic type 1 hepatitis C infection and weighing more than 75 kg were treated with 180 µg of PEG-IFN weekly and 1,200 mg RBV daily for 24 weeks. The patients received RBV dosed as 1,200 mg once-daily for 12 weeks followed by RBV dosed as 600 mg twice-daily for 12 weeks, or vice versa. In addition to the pharmacokinetic profile, the hematological profile and side effects were recorded. The RBV concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry. Results: Eight of twelve patients completed the study. Neither the time taken for RBV to reach peak plasma concentration nor the AUC0-last (adjusted for difference in dose was significantly different between the two groups (P>0.05. Furthermore, the once-daily regimen did not give more side effects than the twice-daily regimen (P>0

  12. A randomized phase III study evaluating the efficacy of single-dose NEPA, a fixed antiemetic combination of netupitant and palonosetron, versus an aprepitant regimen for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC).

    Science.gov (United States)

    Zhang, L; Lu, S; Feng, J; Dechaphunkul, A; Chang, J; Wang, D; Chessari, S; Lanzarotti, C; Jordan, K; Aapro, M

    2018-02-01

    Co-administration of multiple antiemetics that inhibit several molecular pathways involved in emesis is required to optimize chemotherapy-induced nausea and vomiting (CINV) control in patients receiving highly emetogenic chemotherapy (HEC). NEPA, a fixed combination of a highly selective NK1 receptor antagonist, netupitant (300 mg), and the pharmacologically distinct 5-HT3RA, palonosetron (PALO 0.50 mg), has shown superior CINV prevention compared with PALO in cisplatin and anthracycline/cyclophosphamide-based settings. This study is the first head-to-head comparison of NEPA versus an aprepitant (APR)/granisetron (GRAN) regimen. This randomized, double-blind phase III study conducted in Asia was designed with the primary objective to demonstrate non-inferiority of a single oral dose of NEPA compared with a 3-day oral APR/GRAN regimen in chemotherapy-naïve patients receiving cisplatin-based HEC. All patients also received oral dexamethasone (DEX) on days 1-4. The primary efficacy endpoint was complete response (CR: no emesis/no rescue medication) during the overall (0-120 h) phase. Non-inferiority was defined as a lower 95% CI greater than the non-inferiority margin set at - 10%. Secondary efficacy endpoints included no emesis, no rescue medication, and no significant nausea (NSN). Treatment groups were comparable for the 828 patients analyzed: predominantly male (71%); mean age 54.5 years; ECOG 0-1 (98%); lung cancer (58%). NEPA demonstrated non-inferiority to APR/GRAN for overall CR [NEPA 73.8% versus APR/GRAN 72.4%, 95% CI (-4.5%, 7.5%)]. No emesis [NEPA 75.0% versus APR/GRAN 74.0%, 95% CI (-4.8%, 6.9%)] and NSN rates [NEPA 75.7% versus APR/GRAN 70.4%, 95% CI (-0.6%, 11.4%)] were similar between groups, but significantly more NEPA patients did not take rescue medication [NEPA 96.6% versus APR/GRAN 93.5%, 95% CI (0.2%, 6.1%)]. NEPA was well tolerated with a similar safety profile to APR/GRAN. In this first study comparing NK1RA regimens and DEX, NEPA

  13. Applying optimization algorithms to tuberculosis antibiotic treatment regimens.

    Science.gov (United States)

    Cicchese, Joseph M; Pienaar, Elsje; Kirschner, Denise E; Linderman, Jennifer J

    2017-12-01

    Tuberculosis (TB), one of the most common infectious diseases, requires treatment with multiple antibiotics taken over at least 6 months. This long treatment often results in poor patient-adherence, which can lead to the emergence of multi-drug resistant TB. New antibiotic treatment strategies are sorely needed. New antibiotics are being developed or repurposed to treat TB, but as there are numerous potential antibiotics, dosing sizes and potential schedules, the regimen design space for new treatments is too large to search exhaustively. Here we propose a method that combines an agent-based multi-scale model capturing TB granuloma formation with algorithms for mathematical optimization to identify optimal TB treatment regimens. We define two different single-antibiotic treatments to compare the efficiency and accuracy in predicting optimal treatment regimens of two optimization algorithms: genetic algorithms (GA) and surrogate-assisted optimization through radial basis function (RBF) networks. We also illustrate the use of RBF networks to optimize double-antibiotic treatments. We found that while GAs can locate optimal treatment regimens more accurately, RBF networks provide a more practical strategy to TB treatment optimization with fewer simulations, and successfully estimated optimal double-antibiotic treatment regimens. Our results indicate surrogate-assisted optimization can locate optimal TB treatment regimens from a larger set of antibiotics, doses and schedules, and could be applied to solve optimization problems in other areas of research using systems biology approaches. Our findings have important implications for the treatment of diseases like TB that have lengthy protocols or for any disease that requires multiple drugs.

  14. Efficacy and safety of combination therapy with latanoprost after a change in therapeutic regimen from timolol to brinzolamide in Japanese adult patients with primary open-angle glaucoma and ocular hypertension: open, non-randomized 12-week study

    Directory of Open Access Journals (Sweden)

    Shusaku Ishikawa

    2008-09-01

    Full Text Available Shusaku Ishikawa1, Yoshimi Nakamura1, Yuko Nakamura1, Hiroshi Sakai1, Shoichi Sawaguchi1, Kazuo Terashima2, Makoto Kanno2, Hidetoshi Yamashita21Department of Ophthalmology, University of the Ryukyus Faculty of Medicine, Okinawa, Japan; 2Department of Ophthalmology and Visual Science, Yamagata University Faculty of Medicine, Yamagata, JapanPurpose: To compare the efficacy of brinzolamide in Japanese patients with primary open-angle glaucoma (POAG or ocular hypertension (OH after a change from timolol in combination therapy with latanoprost.Methods: A 12-week, prospective, open-label, comparative study was performed in 20 patients [11 males and 9 females, mean age of 64.5 ± 11.0 (SDy] with POAG or OH treated with both latanoprost once daily and timolol 0.5% twice daily. During the study brinzolamide was substituted for timolol. Intraocular pressure (IOP was measured at baseline, 4, 8, and 12 weeks. Blood pressure (BP, pulse rate (PR, and adverse events were also recorded.Results: IOPs at baseline, 4, 8, and 12 weeks were 18.6 ± 2.1 mmHg, 17.8 ± 2.6 mmHg, 17.4 ± 2.5 mmHg, and 17.3 ± 3.5 mmHg, respectively. IOP reduction at 4 and 8 weeks was statistically significant (p < 0.05. The PR was significantly increased at 12 weeks (p < 0.01, but BP was not significantly affected. Four ocular adverse events were noted, but all were mild and transient.Conclusions: Substituting brinzolamide 1% for timolol 0.5% in combination therapy with latanoprost 0.005% demonstrated significant IOP reduction with improvement in PR with POAG or OH. Combination therapy using latanoprost and brinzolamide may be recommended for better IOP control with fewer systemic adverse events.Keywords: open-angle glaucoma, brinzolamide/latanprost combination therapy, timolol/latanoprost combination therapy, intraocular pressure

  15. Selections of appropriate regimen of high-dose chemotherapy combined with adoptive cellular therapy with dendritic and cytokine-induced killer cells improved progression-free and overall survival in patients with metastatic breast cancer: reargument of such contentious therapeutic preferences.

    Science.gov (United States)

    Ren, Jun; Di, Lijun; Song, Guohong; Yu, Jing; Jia, Jun; Zhu, Yuling; Yan, Ying; Jiang, Hanfang; Liang, Xu; Che, Li; Zhang, Jie; Wan, Fengling; Wang, Xiaoli; Zhou, Xinna; Lyerly, Herbert Kim

    2013-10-01

    We hypothesized that combination of dendritic cell (DC) with autologous cytokine-induced killer (CIK) immunotherapy in setting of high-dose chemotherapy (HDC) would be effective for selected metastatic breast cancer (MBC) patients. Our previous work showed thiotepa could eradicate breast cancer stem cells. From 2004 to 2009, 79 patients received standard dose chemotherapy (SDC) of 75 mg/m(2) docetaxel and 75 mg/m(2) thiotepa versus 87 patients of HDC + DC/CIK: 120 mg/m(2) docetaxel to mobilize peripheral CD34(+) progenitor cells, a sequence of HDC (120 mg/m(2) docetaxel, plus 175 mg/m(2) thiotepa) + DC/CIK, with or without 400 mg/m(2) carboplatin depending upon bone marrow function. The endpoints were response rates (RR), progression-free survival (PFS), and overall survival (OS). Compared with SDC, PFS and OS were improved in HDC + DC/CIK (median PFS 10.2 vs. 3.7 months, P < 0.001; median OS 33.1 vs. 15.2 months, P < 0.001). Patients of pre-menopausal, HDC as first-line treatment after metastasis, or with visceral metastasis showed prolonged PFS and OS. SDC group also achieved the similar response as previous reports. Our study demonstrated the novel combination of HDC with DC/CIK to be an effective choice for the selected MBC population, in which choosing appropriate chemo regimens played important roles, and also specific HDC regimen plus DC/CIK immunotherapy showed the clinical benefits compared with chemotherapy alone.

  16. DIOS - database of formalized chemotherapeutic regimens.

    Science.gov (United States)

    Klimes, Daniel; Smid, Roman; Kubasek, Miroslav; Vyzula, Rostislav; Dušek, Ladislav

    2013-01-01

    Chemotherapeutic regimens (CHR) and their administration are routine practice in contemporary oncology. The development of a structured, electronic database of standard CHR can help the faster propagation of information about new CHR and at the same time enable assessment of their adherence in clinical practice. The goal was to develop a standardized way to describe a regimen using XML, fill the database with currently available regimens and develop tools to assess the adherence of the treatment to chosen regimen, compare the dose-intensity and recognize the regimen from existing data on drug administration. The data are being inserted in cooperation with expert oncologists and the database currently contains about 260 CHRs. Such system can be used to enhance decision support systems and interoperability of HIS. The database and tools are available online on the internet.

  17. Optimal HIV Postexposure Prophylaxis Regimen Completion With Single Tablet Daily Elvitegravir/Cobicistat/Tenofovir Disoproxil Fumarate/Emtricitabine Compared With More Frequent Dosing Regimens.

    Science.gov (United States)

    Mayer, Kenneth H; Jones, Daniel; Oldenburg, Catherine; Jain, Sachin; Gelman, Marcy; Zaslow, Shayne; Grasso, Chris; Mimiaga, Matthew J

    2017-08-15

    The study evaluated elvitegravir/cobicistat/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) ("Quad pill") for postexposure prophylaxis (PEP). HIV-exposed individuals may benefit from PEP, but completion rates have been suboptimal because of regimen complexity and side effects. Newer antiretroviral combinations coformulated as single daily pills may optimize PEP adherence. One hundred HIV-uninfected individuals who presented to a Boston community health center after an acute HIV sexual exposure were enrolled and initiated PEP with the daily, single-pill combination Quad pill for a 28-day course. Side effects and medication completion rates from study participants were compared with historical controls who had used PEP regimens consisting of TDF/FTC daily and raltegravir twice daily, or earlier regimens of twice daily zidovudine (AZT)/lamivudine (3TC) and a protease inhibitor, using χ tests for independence. Of the 100 participants who initiated the Quad pill for PEP after a high-risk sexual exposure, 71% completed the 28-day Quad pill regimen, which was significantly greater than historical controls who used TDF/FTC and raltegravir (57%, P pill users were as follows: abdominal discomfort or pain, gas or bloating (42%), diarrhea (38%), fatigue (28%), nausea or vomiting (28%), headache (14%), or dizziness or lightheadedness (6%). Most symptoms were mild, limited, and did not result in medication discontinuation. No participants became HIV infected. Fixed-dose combination of elvitegravir/cobicistat/TDF/FTC was safe and well tolerated for PEP, with higher regimen completion rates than more frequently dosed PEP regimens.

  18. Phase II, Open Label, Randomized Comparative Trial of Ondansetron Alone versus the Combination of Ondansetron and Aprepitant for the Prevention of Nausea and Vomiting in Patients with Hematologic Malignancies Receiving Regimens Containing High-Dose Cytarabine

    Directory of Open Access Journals (Sweden)

    Talha Badar

    2015-01-01

    Full Text Available Background. Aprepitant is a P/neurokinin-1 receptor antagonist approved for the prevention of CINV in moderate emetic risk chemotherapy. We explored its effectiveness in patients with leukemia receiving cytarabine-based chemotherapy. Methods. Patients were randomized to ondansetron (OND 8 mg IV 30 minutes before cytarabine followed by 24 mg IV continuous infusion daily until 6–12 hours after the last dose of chemotherapy alone or with aprepitant (APREP oral 125 mg 6–12 hrs before chemotherapy and 80 mg daily until 1 day after the last dose of chemotherapy. Results. Forty-nine patients were enrolled in each arm; 42 in OND and 41 in OND + APREP arm were evaluable for efficacy. The ORR with OND + APREP was 80% compared to 67% with OND alone (P=0.11. On days 6 and 7, higher proportion of patients treated with OND + APREP were free from nausea (74%, 74% versus 68%, 67%; P=0.27 and 0.18, resp.. Requirement of rescue medications on days 2 and 3 was fewer in OND + APREP arm 7% and 5% compared to 21% and 16% in the OND arm, respectively (P=0.06 and P=0.07. Conclusions. There was a trend for overall improvement in emesis with ondansetron plus aprepitant. The potential benefit of this approach with specific chemotherapy combinations remains to be determined.

  19. A cost comparison of biologic treatment regimens for metastatic colorectal cancer in Italy

    Directory of Open Access Journals (Sweden)

    Sergio Iannazzo

    2017-10-01

    Full Text Available IntroductionBevacizumab is a monoclonal antibody, which, in association with combination chemotherapy regimens, has been shown to be active in metastatic colorectal cancer. Other biologic agents active in the same setting are cetuximab and panitumumab, both of which are monoclonal antibodies directed against the antiepidermal growth factor receptor. The objective of this study was to compare treatment costs of first-line regimens for metastatic colorectal cancer in Italy.MethodsA set of first-line regimens was considered, according to the Italian Association of Medical Oncology and the European Society for Medical Oncology guidelines. A targeted review of the literature was undertaken to identify clinical study references for treatment regimens. The total cost of a regimen was calculated in the perspective of the Italian healthcare system summing up drugs, administration, and adverse event costs, based on year 2016 prices and tariffs.ResultsBevacizumab 7.5 mg + capecitabine was the least expensive regimen, with a total cost of €16,754 per patient. When we consider regimens based on FOLFOX, bevacizumab 5 mg + FOLFOX4 was the least expensive (€32,709 per patient, compared to panitumumab + FOLFOX4 (€42,815, cetuximab + FOLFOX4 (€42,725, and cetuximab + FOLFOX (€37,995. If we consider combination regimens based on FOLFIRI, the association of FOLFIRI and bevacizumab was less expensive than regimens that included cetuximab (€28,389 for bevacizumab 5 mg + FOLFIRI and €35,310 for cetuximab + FOLFIRI.ConclusionsFrom the perspective of the Italian health care system, bevacizumab appears to be a convenient option among the first-line regimens for metastatic colorectal cancer. Further study, based on real-world evidence, would be necessary to confirm this result.

  20. Gonzalez Regimen (PDQ®)—Patient Version

    Science.gov (United States)

    Expert-reviewed information summary about the Gonzalez regimen as a treatment for people with cancer. Note: The information in this summary is no longer being updated and is provided for reference purposes only.

  1. Comparison of antiplatelet regimens in secondary stroke prevention

    DEFF Research Database (Denmark)

    Christiansen, Christine Benn; Pallisgaard, Jannik; Gerds, Thomas Alexander

    2015-01-01

    BACKGROUND: In patients with ischemic stroke of non-cardioembolic origin, acetylsalicylic acid, clopidogrel, or a combination of acetylsalicylic acid and dipyridamole are recommended for the prevention of a recurrent stroke. The purpose of this study was to examine the risk of bleeding or recurrent...... were calculated for each antiplatelet regimen. RESULTS: Among patients discharged after first-time ischemic stroke, 3043 patients were treated with acetylsalicylic acid, 12,295 with a combination of acetylsalicylic acid and dipyridamole, and 3885 with clopidogrel. Adjusted HRs for clopidogrel versus...... the combination of acetylsalicylic acid and dipyridamole were 1.02 (95% confidence interval [CI]: 0.89-1.17) for ischemic stroke and 1.06 (95% CI: 0.83-1.35) for bleeding. Adjusted HRs for acetylsalicylic acid versus the combination of acetylsalicylic acid and dipyridamole were 1.48 (95% CI: 1.31-1.67) for stroke...

  2. Sterilizing Activity of Fully Oral Intermittent Regimens against Mycobacterium Ulcerans Infection in Mice.

    Directory of Open Access Journals (Sweden)

    Aurélie Chauffour

    2016-10-01

    Full Text Available The treatment of Buruli ulcer (BU that is caused by Mycobacterium ulcerans, is currently based on a daily administration of rifampin and streptomycin (RIF-STR. A fully oral intermittent regimen would greatly simplify its treatment on the field.The objective of this study was to assess the bactericidal and sterilizing activities of intermittent oral regimens in a murine model of established M. ulcerans infection. Regimens combining rifapentine (RFP 20 mg/kg with either moxifloxacin (MXF 200 mg/kg, clarithromycin (CLR 100 mg/kg or bedaquiline (BDQ 25 mg/kg were administrated twice (2/7 or three (only for RFP-CLR 3/7 times weekly during 8 weeks. The bactericidal but also the sterilizing activities of these four intermittent oral regimens were at least as good as those obtained with control weekdays regimens, i.e. RFP-CLR 5/7 or RIF-STR 5/7. A single mouse from the RFP-MFX 2/7 group had culture-positive relapse at the end of the 28 weeks following treatment completion among the 157 mice treated with one of the four intermittent regimens (40 RFP-CLR 2/7, 39 RFP-CLR 3/7, 39 RFP-MXF 2/7, 39 RFP-BDQ 2/7.These results open the door for a fully intermittent oral drug regimen for BU treatment avoiding intramuscular injections and facilitating supervision by health care workers.

  3. Sterilizing Activity of Fully Oral Intermittent Regimens against Mycobacterium Ulcerans Infection in Mice.

    Science.gov (United States)

    Chauffour, Aurélie; Robert, Jérôme; Veziris, Nicolas; Aubry, Alexandra; Jarlier, Vincent

    2016-10-01

    The treatment of Buruli ulcer (BU) that is caused by Mycobacterium ulcerans, is currently based on a daily administration of rifampin and streptomycin (RIF-STR). A fully oral intermittent regimen would greatly simplify its treatment on the field. The objective of this study was to assess the bactericidal and sterilizing activities of intermittent oral regimens in a murine model of established M. ulcerans infection. Regimens combining rifapentine (RFP 20 mg/kg) with either moxifloxacin (MXF 200 mg/kg), clarithromycin (CLR 100 mg/kg) or bedaquiline (BDQ 25 mg/kg) were administrated twice (2/7) or three (only for RFP-CLR 3/7) times weekly during 8 weeks. The bactericidal but also the sterilizing activities of these four intermittent oral regimens were at least as good as those obtained with control weekdays regimens, i.e. RFP-CLR 5/7 or RIF-STR 5/7. A single mouse from the RFP-MFX 2/7 group had culture-positive relapse at the end of the 28 weeks following treatment completion among the 157 mice treated with one of the four intermittent regimens (40 RFP-CLR 2/7, 39 RFP-CLR 3/7, 39 RFP-MXF 2/7, 39 RFP-BDQ 2/7). These results open the door for a fully intermittent oral drug regimen for BU treatment avoiding intramuscular injections and facilitating supervision by health care workers.

  4. Differences in Lipid Measurements by Antiretroviral Regimen Exposure in Cohorts from Asia and Australia

    Directory of Open Access Journals (Sweden)

    Amit C. Achhra

    2012-01-01

    Full Text Available We explored the mean differences in routinely measured lipids (total cholesterol, triglycerides, and high-density lipoprotein cholesterol according to exposure to different combination antiretroviral regimens in Asian (n=2051 and Australian (predominantly Caucasian, n=794 cohorts. The regimen was defined as at least 3 antiretroviral drugs with at least 2 nucleoside-reverse transcriptases (NRTIs and either of at least one protease inhibitor (PI or non-nucleoside-reverse transcriptases (NNRTIs. We categorised cART regimens as: NRTIs as tenofovir based or not; NNRTIs as nevirapine or efavirenz (but not both; and PI as atazanavir based or not. We found that the impact of various antiretroviral regimens on lipids in Asian and Australian cohorts was only different by cohort for total cholesterol (P for interaction between regimen and cohort: 0.05. The differences in total cholesterol were however small and unlikely to be of clinical significance. Overall, tenofovir with nevirapine or atazanavir was associated with the most favorable lipids, while the PI regimens without tenofovir and atazanavir were associated with least favorable lipids. We conclude that the impact of various ART regimens on lipids is largely similar in Asian and Australian cohorts and that the newer drugs such as tenofovir and atazanavir are likely to provide similar benefit in terms of lipid profiles in both populations.

  5. Abacavir-based triple nucleoside regimens for maintenance therapy in patients with HIV.

    Science.gov (United States)

    Cruciani, Mario; Mengoli, Carlo; Serpelloni, Giovanni; Parisi, Saverio G; Malena, Marina; Bosco, Oliviero

    2013-06-05

    Regimen simplification can be defined as a change in established effective therapy to reduce pill burden and dosing frequency, to enhance tolerability, or to decrease specific food and fluid requirements. Many patients on suppressive antiretroviral therapy may be considered candidates for a simplification strategy and, among them, those who have achieved virologic suppression. Several clinical trials have evaluated the efficacy of triple nucleoside combination as a simplification therapy in patients who achieved virologic suppression The aim of this review is to combine randomised, controlled trials to examine whether in patients with undetectable viraemia on a Protease inhibitor (PI) based regimen simplification treatment with abacavir (ABC)-based triple-nucleoside combinations has similar rates of efficacy and tolerability compared with a PI regimen or simplification with a NNRTIs (efavirenz-EFV- or nevirapine-NVP) containing regimen. Studies were included if they had at least two of the three interventions, including one 3NRTI arm. Electronic databases and conference proceedings were searched (1996-2012) with relevant search terms without limits to language. Randomised controlled trials (RCTs) only are included in this review. Patients population is represented by HIV-infected adult patients treated with a PI-containing regimen (PI or boosted PI),  with undetectable viral load. Patients on a PI-containing regimen had three possibilities: continue the PI regimen or switch to a simplification maintenance regimen, including switch to a NNRTI (EFV or NVP) containing regimen, or switch to a triple-NRTI regimen (ABC-zidovudine-lamivudine) The primary outcomes were: proportion of patients discontinuing or switching antiretroviral therapy due to virologic failure or to adverse events; death (all cause) and AIDS defining illness; occurrence of myocardial infarction and cardiovascular disease. Secondary outcomes  were: proportion of patients maintaining an undetectable

  6. [ADOC regimen for unresectable advanced thymic cancer].

    Science.gov (United States)

    Koizumi, T; Takabayashi, Y; Yamagishi, S; Tsushima, K; Takamizawa, A; Takashi, S; Tsukadaira, A; Masubuchi, T; Yamamoto, H; Kaneki, T; Yamaguchi, S; Hachiya, T; Hayasaka, M; Fujimoto, K; Kubo, K

    1999-12-01

    Between 1996 and 1998, we treated 6 patients with unresectable and advanced thymic cancer (stages IVa and IVb). All received 50 mg/m2 of cisplatin and 40 mg/m2 of doxorubicin intravenously (i.v.) on day 1,0.6 mg/m2 of vincristine i.v. on day 3, and 700 mg/m2 of cyclophosphamide i.v. on day 4; ADOC regimen, respectively at 3-4 week intervals. Four patients obtained a partial response (PR) after ADOC chemotherapy and the overall clinical response rate was 67%. No life-threatening side effects were noted. In 2 patients, cisplatin plus VP-16 chemotherapy failed to demonstrate any benefits prior to the ADOC regimen. Radiotherapy was initiated after the achievement of PR in the other 2 patients. ADOC chemotherapy appears to be an effective treatment for thymic cancer.

  7. New Treatment Regimen for Latent Tuberculosis Infection

    Centers for Disease Control (CDC) Podcasts

    2012-03-15

    In this podcast, Dr. Kenneth Castro, Director of the Division of Tuberculosis Elimination, discusses the December 9, 2011 CDC guidelines for the use of a new regimen for the treatment of persons with latent tuberculosis infection.  Created: 3/15/2012 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 3/15/2012.

  8. Desfechos clínicos do tratamento de tuberculose utilizando o esquema básico recomendado pelo Ministério da Saúde do Brasil com comprimidos em dose fixa combinada na região metropolitana de Goiânia Clinical treatment outcomes of tuberculosis treated with the basic regimen recommended by the Brazilian National Ministry of Health using fixed-dose combination tablets in the greater metropolitan area of Goiânia, Brazil

    Directory of Open Access Journals (Sweden)

    Anna Carolina Galvão Ferreira

    2013-02-01

    Full Text Available OBJETIVO: Descrever as taxas de cura, falência e abandono do tratamento da tuberculose com o esquema básico preconizado pelo Ministério da Saúde (tratamento com rifampicina, isoniazida, pirazinamida e etambutol por dois meses seguido de isoniazida e rifampicina por quatro meses utilizando comprimidos em dose fixa combinada em regime autoadministrado e descrever os eventos adversos e seus possíveis impactos nos desfechos do tratamento. MÉTODOS: Estudo descritivo utilizando dados coletados prospectivamente dos prontuários médicos de pacientes com tuberculose (idade > 18 anos tratados com o esquema básico em duas unidades básicas de saúde da região metropolitana de Goiânia, GO. RESULTADOS: A amostra foi composta por 40 pacientes com tuberculose. A taxa de cura foi de 67,5%, a taxa de abandono foi de 17,5%, e não ocorreram casos de falência. Nessa amostra, 19 pacientes (47% relataram reações adversas aos medicamentos. Essas foram leves e moderadas, respectivamente, em 87% e 13% dos casos. Em nenhum caso houve necessidade de mudança do esquema ou suspensão do tratamento. CONCLUSÕES: A taxa de cura do esquema básico com o uso de comprimidos em dose fixa combinada sob regime autoadministrado foi semelhante às taxas históricas do esquema anterior. A taxa de abandono, na amostra estudada, foi muito acima da taxa preconizada como adequada (até 5%.OBJECTIVE: To describe the rates of cure, treatment failure, and treatment abandonment obtained with the basic regimen recommended by the Brazilian National Ministry of Health (rifampin, isoniazid, pyrazinamide, and ethambutol for two months, followed by isoniazid and rifampin for four months involving the use of fixed-dose combination tablets (self-administered treatment, as well as to describe adverse events and their potential impact on treatment outcomes. METHODS: This was a descriptive study based on prospective data obtained from the medical records of tuberculosis patients (> 18

  9. Repeated Courses of Rituximab in Chronic ITP: Three Different Regimens

    Science.gov (United States)

    Hasan, Aisha; Michel, Marc; Patel, Vivek; Stasi, Roberto; Cunningham-Rundles, Susanna; Leonard, John; Bussel, James

    2009-01-01

    This study investigated responses to re-treatment with rituximab in chronic ITP patients. Treatment with rituximab in chronic ITP patients induces long-lasting responses in approximately 30% of patients but even these patients may relapse. Twenty patients who had achieved a response to rituximab and relapsed were re-treated with rituximab (375 mg/m2 × 4); this data was analyzed retrospectively. Subsequently, 16 patients were prospectively randomized to receive rituximab with CVP (R-CVP) or double dose rituximab (DDR). Re- treatment with standard dose rituximab demonstrated responses similar to initial rituximab treatment in 15 of 20 patients. Neither of the 2 more intensive regimens (R-CVP, DDR) induced responses in any patient who had previously failed to respond to rituximab nor induced substantially longer-lasting responses among previous responders. No additional toxicity was noted with the DDR regimen, whereas R-CVP was not well tolerated. These results suggest that re-treatment with standard dose rituximab induces similar responses in 75% of previously responding patients and is well tolerated. Neither combining rituximab with CVP nor doubling the dose of rituximab increased the response rate. PMID:19731307

  10. Commonly Prescribed Antiretroviral Therapy Regimens and Incidence of AIDS-Defining Neurological Conditions

    NARCIS (Netherlands)

    Caniglia, Ellen C.; Phillips, Andrew; Porter, Kholoud; Sabin, Caroline A.; Winston, Alan; Logan, Roger; Gill, John; Vandenhende, Marie-Anne; Barger, Diana; Lodi, Sara; Moreno, Santiago; Arribas, José Ramón; Pacheco, Antonio; Cardoso, Sandra W.; Chrysos, George; Gogos, Charalabos; Abgrall, Sophie; Costagliola, Dominique; Meyer, Laurence; Seng, Remonie; van Sighem, Ard; Reiss, Peter; Muga, Roberto; Hoyos, Santiago Pérez; Braun, Dominique; Hauser, Christoph; Barrufet, Pilar; Leyes, Maria; Tate, Janet; Justice, Amy; Hernán, Miguel A.

    2018-01-01

    The differential effects of commonly prescribed combined antiretroviral therapy (cART) regimens on AIDS-defining neurological conditions (neuroAIDS) remain unknown. Prospective cohort studies of HIV-positive individuals from Europe and the Americas included in the HIV-CAUSAL Collaboration.

  11. Comparison of two dose regimens of misoprostol for second-trimester pregnancy termination

    NARCIS (Netherlands)

    Brouns, Joseph Franciscus Gertrudis Maria; van Wely, Madelon; Burger, Mattheus Petrus Maria; van Wijngaarden, Willem Jacobus

    2010-01-01

    Objective: The study was conducted to compare the efficacy of two different dose regimens of misoprostol administered vaginally in combination with mifepristone for second trimester termination of viable and non-viable pregnancies. Design: Double-blind randomized controlled trial conducted at the

  12. Dyslipidemia in an Asian population after treatment for two years with protease inhibitor-containing regimens

    NARCIS (Netherlands)

    Kerr, Stephen J.; Duncombe, Chris; Avihingsanon, Anchalee; Ananworanich, Jintanat; Boyd, Mark; Sopa, Bunruan; Medtech, B.; Chuenyam, Theshinee; Cooper, David A.; Lange, Joep M. A.; Phanuphak, Praphan; Ruxrungtham, Kiat

    2007-01-01

    There are limited data about dyslipidemia in Asian patients treated with combination antiretroviral therapy. To assess the relative association of different protease-inhibitor-containing regimens with the degree of dyslipidemia, fasting lipid levels were compared during 110 weeks in 250

  13. A Systematic Review of Recall Regimen and Maintenance Regimen of Patients with Dental Restorations. Part 2: Implant-Borne Restorations.

    Science.gov (United States)

    Bidra, Avinash S; Daubert, Diane M; Garcia, Lily T; Gauthier, Marissa F; Kosinski, Timothy F; Nenn, Conrad A; Olsen, John A; Platt, Jeffrey A; Wingrove, Susan S; Chandler, Nancy Deal; Curtis, Donald A

    2016-01-01

    To evaluate the current scientific evidence on patient recall and maintenance of implant-supported restorations, to standardize patient care regimens and improve maintenance of oral health. An additional purpose was to examine areas of deficiency in the current scientific literature and provide recommendations for future studies. An electronic search for articles in the English language literature from the past 10 years was performed independently by multiple investigators using a systematic search process. After application of predetermined inclusion and exclusion criteria, the final list of articles was reviewed to meet the objectives of this review. The initial electronic search resulted in 2816 titles. The systematic application of inclusion and exclusion criteria resulted in 14 articles that satisfied the study objectives. An additional 6 articles were added through a supplemental search process for a total of 20 studies. Of these, 11 were randomized controlled clinical trials, and 9 were observational studies. The majority of the studies (15 out of 20) were conducted in the past 5 years and most studies were conducted in Europe (15), followed by Asia (2), South America (1), the United States (1), and the Middle East (1). Results from the qualitative data on a combined 1088 patients indicated that outcome improvements in recall and maintenance regimen were related to (1) patient/treatment characteristic (type of prosthesis, type of prosthetic components, and type of restorative materials); (2) specific oral topical agents or oral hygiene aids (electric toothbrush, interdental brush, chlorhexidine, triclosan, water flossers) and (3) professional intervention (oral hygiene maintenance, and maintenance of the prosthesis). There is minimal evidence related to recall regimens in patients with implant-borne removable and fixed restorations; however, a considerable body of evidence indicates that patients with implant-borne removable and fixed restorations require

  14. Partnerships to Design Novel Regimens to Treat Childhood Tuberculosis, Sui Generis: The Road Ahead.

    Science.gov (United States)

    Gumbo, Tawanda; Makhene, Mamodikoe K; Seddon, James A

    2016-11-01

    There has been a recent expansion of preclinical models to predict the efficacy of regimens to treat adults with tuberculosis. Despite increasing global interest in childhood tuberculosis, these same tools have not been employed to develop pediatric regimens. Children differ from adults in bacillary burden, spectrum of disease, the metabolism and distribution of antituberculosis drugs, and the toxicity experienced. The studies documented in this series describe a proof-of-concept approach to pediatric regimen development. We propose a program of investigation that would take this forward into a systematic and comprehensive method to find optimal drug combinations to use in children, ideal exposures, and required dosing. Although the number of possible drug combinations is extensive, a series of principles could be employed to select likely effective regimens. Regimens should avoid drugs with overlapping toxicity or linked mechanisms of resistance and should aim to include drugs with different mechanisms of action and ones that are able to target different subpopulations of mycobacteria. Finally drugs should penetrate into body sites necessary for treating pediatric disease. At an early stage, this body of work would need to engage with regulatory agencies and bodies that formulate guidelines, so that once regimens and dosages are identified, translation into clinical studies and clinical practice can be rapid. The development of child-friendly drug formulations would need to be carried out in parallel so that pharmacokinetic studies can be undertaken as formulations are created. Significant research and development would be required and a wide range of stakeholders would need to be engaged. The time is right to consider a more thoughtful and systematic approach toward identifying, testing, and comparing combinations of drugs for children with tuberculosis. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  15. Effectiveness of a sanguinarine regimen after scaling and root planing.

    Science.gov (United States)

    Tenenbaum, H; Dahan, M; Soell, M

    1999-03-01

    A variety of chemical agents have been evaluated relative to their abilities to inhibit dental plaque and to improve gingival health. Chlorhexidine gluconate is the best known and most widely used member of these agents, but its long-term use is compromised by different side effects, especially extrinsic tooth and tongue staining. Another agent, sanguinarine, which is currently used in both a mouthrinse and toothpaste, leads in some cases only to a transient burning sensation and could be used on a long-term basis. The purpose of this 14-week controlled clinical trial was to assess the effectiveness of a toothpaste and oral rinse containing sanguinaria extract after scaling, root planing and a chlorhexidine regimen. Sixty patients diagnosed as having adult periodontitis received initial periodontal therapy including scaling and root planing, followed by a 2-week oral care regimen which included rinsing with 0.2% chlorhexidine gluconate oral rinse. Upon completion of this 2-week initial therapy phase, patients were randomly assigned to either sanguinarine toothpaste and oral rinse or to control toothpaste and oral rinse without sanguinarine. Plaque (modified Quigley-Hein index) and gingivitis (gingival index) were measured prior to periodontal therapy, at the end of the chlorhexidine phase (2 weeks), and after 8 and 14 weeks. Sanguinarine-containing toothpaste and oral rinse significantly inhibited the redevelopment of gingivitis through the 12 weeks following the chlorhexidine phase compared to the control toothpaste and rinse. Patients in the test group had 26% fewer bleeding sites at 8 weeks, and 32% fewer at 14 weeks, than the control group. Our results support the combined use of chlorhexidine mouthrinse for a short term (2 weeks) followed by sanguinaria mouthrinse and toothpaste up to 3 months in order to optimize the effectiveness of chlorhexidine without side effects. Further studies on the long-term effect of this combination should be established.

  16. Characterization of HIV-1 from patients with virological failure to a boosted protease inhibitor regimen

    DEFF Research Database (Denmark)

    Lillemark, Marie Rathcke; Gerstoft, Jan; Obel, Niels

    2011-01-01

    The use of highly active antiretroviral treatment (HAART) regimens with unboosted protease inhibitors (PIs) has resulted in a high level of virological failure primarily due to the development of resistant virus. Current boosted PI regimens combine successfully low-dose ritonavir (r) with a second...... PI. The aim of the study was to estimate the proportion of patients, in a population based setting, who develop virological failure on a PI/r regimen. Through The Danish HIV Cohort Study 1,007 patients who received PI/r based treatment between 1995 and 2008 were identified. Twenty-three (2.......3%) experienced virological failure, of whom 19 (83%) started PI/r treatment before 2001. Patients from Copenhagen (n=19) were selected to study the development of protease (PR) and gag cleavage site (CS) mutations during PI/r treatment and PI plasma levels at the time of virological failure. Three patients (16...

  17. Comparison of FOLFOX and DOF regimens as first-line treatment in East Asian patients with advanced gastric cancer.

    Science.gov (United States)

    Liu, Mengyao; Hu, Guofang; Wang, Yuan; Guo, Jun; Liu, Liyan; Han, Xiao; Wang, Zhehai

    2018-01-01

    Our study retrospectively assesses the safety and efficacy of the FOLFOX (oxaliplatin, fluorouracil, and leucovorin) versus DOF (docetaxel, oxaliplatin, and fluorouracil) regimens in untreated locally advanced gastric cancer (AGC). A total of 108 patients underwent DOF (N=58) and FOLFOX (N=50) regimens. The end points were overall response rate (ORR), survival, and toxicity. Kaplan-Meier curve was used to estimate overall survival (OS) and progression-free survival (PFS) and Cox regression for multivariate analysis. The ORRs were 50% for DOF and 30% for FOLFOX groups ( P DOF group were significantly better than FOLFOX group (8.2 versus 6.4 months, P DOF group (10.3% versus 2%, P DOF also resulted in a superior PFS (8.5 versus 5.9 months; P =0.038) and OS (15.3 versus 9.8 months; P =0.004) compared with FOLFOX. However, DOF regimen was associated with more neutropenia (67% versus 30%; P DOF regimen was more effective than FOLFOX for AGC, both in younger and older patients. The adverse effects of the two regimens were manageable. The combination of docetaxel/oxaliplatin/fluorouracil was active and well tolerated in AGC patients and deserves further evaluation. However, for elderly patients with AGC, the DOF regimen was associated with worse toxicities; therefore, the FOLFOX regimen might be a more suitable option.

  18. Gemcitabine and Vinorelbine (GemVin) Regimen.

    Science.gov (United States)

    Shang, Elizabeth Y; Solimando, Dominic A; Waddell, J Aubrey

    2014-06-01

    The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net.

  19. Prophylactic antibiotic regimens in tumour surgery (PARITY)

    DEFF Research Database (Denmark)

    Petersen, Michael Mørk; Hettwer, Werner H; Grum-Schwensen, Tomas

    2015-01-01

    (44 men and 16 women) across 21 sites from four countries over 24 months (mean 2.13 participants per site per year, standard deviation 2.14). One participant was lost to follow-up and one withdrew consent. Complete data were obtained for 98% of eligible patients at two weeks, 83% at six months, and 73......OBJECTIVE: Clinical studies of patients with bone sarcomas have been challenged by insufficient numbers at individual centres to draw valid conclusions. Our objective was to assess the feasibility of conducting a definitive multi-centre randomised controlled trial (RCT) to determine whether a five...... to conceal treatment allocation and sham antibiotics to blind participants, surgeons, and data collectors. We determined feasibility by measuring patient enrolment, completeness of follow-up, and protocol deviations for the antibiotic regimens. RESULTS: We screened 96 patients and enrolled 60 participants...

  20. Systemic combination treatment for psoriasis: a review

    DEFF Research Database (Denmark)

    Jensen, Peter; Skov, Lone; Zachariae, Claus

    2010-01-01

    exist for the use of systemic combination therapy. Therefore, our aim was to review the current literature on systemic anti-psoriatic combination regimens. We searched PubMed and identified 98 papers describing 116 studies (23 randomized) reporting on the effect of various systemic combination...... treatments. The most thoroughly investigated combination was retinoid and phototherapy. Further controlled research is needed to define the safest and most effective combination regimens....

  1. Impacts of 12-dose regimen for latent tuberculosis infection: Treatment completion rate and cost-effectiveness in Taiwan.

    Science.gov (United States)

    Huang, Yi-Wen; Yang, Shun-Fa; Yeh, Yen-Po; Tsao, Thomas Chang-Yao; Tsao, Shih-Ming

    2016-08-01

    Treatment of latent tuberculosis infection (LTBI) is essential for eradicating tuberculosis (TB). Moreover, the patient adherence is crucial in determining the effectiveness of TB control. Isoniazid given by DOTS daily for 9 months (9H) is the standard treatment for LTBI in Taiwan. However, the completion rate is low due to the long treatment period and its side effects. The combined regimen using a high dose of rifapentine/isoniazid once weekly for 12 weeks (3HP) has been used as an alternative treatment option for LTBI in the United States. This may result in a higher completion rate. In this pilot study, patient adherence and cost of these 2 treatment regimens were investigated. Thus, we aimed to assess the treatment completion rate and costs of 3HP and compare to those with 9H.Data from 691 cases of LTBI treatments including 590 cases using the conventional regimen and 101 cases with rifapentine/Isoniazid were collected. The cost was the sum of the cost of treatment with Isoniazid for 9 months or with rifapentin/Isoniazid for 3 months of all contacts. The effectiveness was the cost of cases of tuberculosis avoided.In this study, the treatment completion rate for patients prescribed with the 3 months rifapentine/isoniazid regimen (97.03%) was higher than those given the conventional 9-month isoniazid regimen (87.29%) (P tuberculosis and US$ 5225/avoided 1 case of tuberculosis with 3HP. In addition, when compared with the conventional regimen, there were fewer patients discontinued with rifapentine/isoniazid regimen due to undesirable side effects.This was the first study to compare the 2 treatment regimens in Taiwan, and it showed that a short-term high-dosage rifapentine/isoniazid treatment regimen reduced costs and resulted in higher treatment completion than the standard LTBI isoniazid treatment.

  2. A novel ceftazidime/avibactam, rifabutin, tedizolid and moxifloxacin (CARTM) regimen for pulmonary Mycobacterium avium disease.

    Science.gov (United States)

    Deshpande, Devyani; Srivastava, Shashikant; Pasipanodya, Jotam G; Lee, Pooi S; Gumbo, Tawanda

    2017-09-01

    To compare the efficacy of ceftazidime/avibactam plus tedizolid-based combination regimens with the standard therapy of azithromycin, ethambutol and rifabutin for the treatment of pulmonary Mycobacterium avium complex (MAC) disease. We mimicked the human pulmonary concentration-time profiles of ceftazidime/avibactam and tedizolid in combination, ceftazidime/avibactam, rifabutin, tedizolid and moxifloxacin (CARTM), and the standard regimen and examined microbial kill in triplicate hollow-fibre system model of intracellular pulmonary MAC (HFS-MAC) units. The tedizolid and moxifloxacin doses used were non-optimized; the tedizolid dose was that associated with bacteriostasis. Drugs were administered daily for 28 days. Each HFS-MAC was sampled in the central and peripheral compartment to ascertain that the intended drug exposures had been achieved. The peripheral compartments were sampled at regular intervals over the 28 days to quantify the burden of MAC. MAC-infected macrophages in the HFS-MAC achieved multi-fold higher intracellular versus extracellular concentrations of rifabutin, moxifloxacin, ceftazidime/avibactam. The non-optimized ceftazidime/avibactam plus tedizolid dual therapy held the bacterial burden at the same level as day 0 (stasis) throughout the 28 days. The standard therapy reduced the bacterial load 2 log10 cfu/mL below stasis on day 14 but started failing after that. The CARTM regimen achieved 3.2 log10 cfu/mL kill below stasis on day 21, but had started to fail by day 28. The CARTM regimen promises to have kill rates better than standard therapy. Experiments to identify exposures of each of the four drugs associated with optimal effect in the CARTM combination are needed in order to design a short-course chemotherapy regimen. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Inappropriate Tuberculosis Treatment Regimens in Chinese Tuberculosis Hospitals

    NARCIS (Netherlands)

    Xue He, Guang; van den Hof, Susan; van der Werf, Marieke J.; Guo, Hui; Hu, Yuan Lian; Fan, Ji Huan; Zhang, Wei Min; Tostado, Christopher P.; Borgdorff, Martien W.

    2011-01-01

    This investigation of tuberculosis (TB) treatment regimens in 6 TB hospitals in China showed that only 18% of patients with new cases and 9% of patients with retreatment cases were prescribed standard TB treatment regimens. Adherence to treatment guidelines needs to be improved in TB hospitals to

  4. The Sex Res Non Naturales and the Regimen of Health

    DEFF Research Database (Denmark)

    Agerholm, Frank Juul

    The paper discusses the ethical and social soundness of the classical idea of diaita/regimen vis-à-vis the contemporary focus on healthy lifestyle......The paper discusses the ethical and social soundness of the classical idea of diaita/regimen vis-à-vis the contemporary focus on healthy lifestyle...

  5. Impact of Anesthetic Regimen on Remote Ischemic Preconditioning in the Rat Heart In Vivo.

    Science.gov (United States)

    Behmenburg, Friederike; van Caster, Patrick; Bunte, Sebastian; Brandenburger, Timo; Heinen, André; Hollmann, Markus W; Huhn, Ragnar

    2018-04-01

    Remote ischemic preconditioning (RIPC) seems to be a promising cardioprotective strategy with contradictive clinical data suggesting the anesthetic regimen influencing the favorable impact of RIPC. This study aimed to investigate whether cardio protection by RIPC is abolished by anesthetic regimens. Male Wistar rats were randomized to 6 groups. Anesthesia was either maintained by pentobarbital (Pento) alone or a combination of sevoflurane (Sevo) and remifentanil or propofol (Prop) and remifentanil in combination with and without RIPC. RIPC reduced infarct size in Pento- and Sevo-anesthetized rats (Pento-RIPC: 30% ± 9% versus Pento-control [Con]: 65% ± 6%, P < .001; Sevo-RIPC: 31% ± 6% versus Sevo-Con: 61% ± 8%, P < .001), but RIPC did not initiate cardio protection in Prop-anesthetized animals (Prop-RIPC: 59% ± 6% versus Prop-Con: 59% ± 8%, P = 1.000). Cardio protection by RIPC is abolished by Prop.

  6. Oral antidiabetic therapy in a large Italian sample: drug supply and compliance for different therapeutic regimens

    CERN Document Server

    Vittorino Gaddi, A; Capello, F; Di Pietro, C; Cinconze, E; Rossi, E; De Sando, V; Cevenini, M; D'Alò, G

    2014-01-01

    Objectives: To define the main features of patients treated with oral antidiabetics, evaluating monotherapy (MT), loose-dose combination therapy (LDCT) and fixed-dose combination therapy (FDCT); to describe medication adherence to the different therapies; and to evaluate the differences in compliance with the prescribed therapy regimen among prevalent and incident patient cohorts. Study design: This study was a retrospective cohort analysis based on the ARNO database, a national record that tracks reimbursable prescription claims submitted from selected pharmacies to the Italian national health system. In total, 169,375 subjects, from an overall population of 4,040,624 were included in this study. The patients represented 12 different local health units. Each patient had at least one oral antidiabetic prescription claim (A10B ATC code). Methods: Patients were divided into four groups according to their treatment regimen during the recruitment period (1 January 2008-31 December 2008): MT, FDCT, LDCT and swi...

  7. An evaluation of the efficacy and toxicity of the MACOP-B regimen alone and in combination with radiotherapy for advanced, aggressive non-Hodgkin`s lymphoma; Ocena skutecznosci i toksycznosci chemioterapii MACOP-B stosowanej samodzielnie i w skojarzeniu z radioterapia u chorych na zaawansowane chloniaki nieziarnicze o posrednim i wiekszym stopniu zlosliwosci

    Energy Technology Data Exchange (ETDEWEB)

    Skolyszewski, J.; Radkowski, A.; Korzeniowski, S.; Migdal, K.; Rys, J. [Centrum Onkologii, Instytut im. M. Sklodowskiej-Curie, Cracow (Poland)

    1994-12-31

    24 patients with clinically advanced and histologically aggressive non-Hodgkin`s lymphoma received MACOP-B chemotherapy. 18 patients completed the full course of chemotherapy, 9 patients also received consolidation limited-field radiation therapy. Twelve out of 18 eligible patients (66.7%) achieved a complete remission (CR) after chemotherapy, and further 2 patients achieved a subsequent CR after consolidation therapy. Total CR rate was 77.8%. The absolute 3-year survival rate was 33.3% in the group of all 24 patients treated. The results confirm the effectiveness of the MACOP-B regimen for patients with advanced, aggressive non-Hodgkin`s lymphoma. MACOP-B is however toxic, and should be modified, especially for patients older than 60 years of age. (author). 14 refs, 2 figs, 5 tabs.

  8. Different oral corticosteroid regimens for acute asthma.

    Science.gov (United States)

    Normansell, Rebecca; Kew, Kayleigh M; Mansour, George

    2016-05-13

    between a higher dose or longer course and a lower dose or shorter course of prednisolone or dexamethasone, or between prednisolone and dexamethasone.Included studies were generally of reasonable methodological quality. Review authors assessed most outcomes in the review as having low or very low quality, meaning we are not confident in the effect estimates. The predominant reason for downgrading was imprecision, but indirectness and risk of bias also reduced our confidence in some estimates. Evidence is not strong enough to reveal whether shorter or lower-dose regimens are generally less effective than longer or higher-dose regimens, or indeed that the latter are associated with more adverse events. Any changes recommended for current practice should be supported by data from larger, well-designed trials. Varied study design and outcome measures limited the number of meta-analyses that we could perform. Greater emphasis on palatability and on whether some regimens might be easier to adhere to than others could better inform clinical decisions for individual patients.

  9. Polypharmacy: correlations with sex, age and drug regimen

    DEFF Research Database (Denmark)

    Bjerrum, L; Søgaard, J; Hallas, J

    1998-01-01

    day, 8.3% of the population were exposed to minor PP and 1.2% to major PP. The prevalence of PP increased with age, and from the age of 70 years, two thirds of all drug users were PP users. Drug use was 50% more prevalent among women than men, but over the age of 70, the sexes did not differ...... therapeutic class (second level of the ATC code) was used as an indicator for the type of health problem. A stepwise backwards logistic regression was used to identify predictors of major PP. Odds ratios were calculated for different drug classes, and the age and sex of all drug users. RESULTS: On a random...... in the prevalence of major PP. Many different drug combinations were found, and among major PP users (n = 5443), two thirds had their own unique drug regimen, different from all other drug users. Cardiovascular drugs and analgesics were often involved in PP among the elderly, while asthma drugs, psychotropic drugs...

  10. High-dose chemotherapy in high-risk myelodysplastic syndrome: covariate-adjusted comparison of five regimens.

    Science.gov (United States)

    Beran, M; Shen, Y; Kantarjian, H; O'Brien, S; Koller, C A; Giles, F J; Cortes, J; Thomas, D A; Faderl, S; Despa, S; Estey, E H

    2001-10-15

    Antileukemic chemotherapy has been used for two decades to treat high-risk myelodysplastic syndrome (refractory anemia with excess of blasts [RAEB] and RAEB in transformation into acute leukemia [RAEB-t]) patients. Because the results of standard regimens have been disappointing, high-dose chemotherapeutic regimens were investigated recently. In the absence of randomized trials, the relative merits of various treatment regimens are unknown. The authors analyzed the outcome for 394 newly diagnosed patients treated between 1991 and 1999 with five regimens consisting of intermediate- or high-dose cytosine arabinoside (A) in combination with idarubicin (I), and introduced cyclophosphamide (C) and the new agents fludarabine (F) and topotecan (T) into new combinations with A. In addition to defining the role of high-intensity chemotherapy in the overall outcome for patients with RAEB-t and RAEB, the authors determined the relative merits of the five regimens (IA, FA, FAI, TA, and CAT), accounting for the nonrandom distribution of the prognostic covariates. The overall complete response (CR) rate of 58% was significantly associated with karyotype, performance status (PS), treatment in the laminar air flow room, duration of antecedent hematologic disorder and age, but not French-American-British or International Prognostic Scoring System risk categories. Multivariate analysis did not identify statistically significant differences in CR rates obtained with each regimen. Induction death rates increased with age with all but the TA regimen; they were lowest with TA (5.4%) and highest with FAI (20.7%), and these differences were significant in patients older than 65 years. The trend for time to death was the same as for time to recurrence in all groups. Multivariate analysis of time to death identified treatment regimen (FA, FAI, and CAT), cytogenetic status (-5/-7), increasing age, and PS greater than 2 as significant independent unfavorable prognostic factors. After

  11. [Choice of initial regimen for antiretroviral-naïve HIV patients: Analysis of motivation].

    Science.gov (United States)

    Rouveix, E; Mortier, E; Beauchet, A; Dupont, C; Gerbe, J; Daneluzzi, V; Brazille, P; Berthe, H; Zucman, D; Genet, P; Simonpoli, A-M; de Truchis, P

    2016-12-01

    Several therapeutic combination antiretroviral therapy regimen are available for initial treatment in naïve HIV infected patients. The choice of a particular regimen remains often subjective. The aim of this study was to determine factors associated with the choice of molecules in initial ARV prescriptions. From 01/01 to 30/10/2014, every initial cART prescription was analyzed regarding patients and physicians characteristics. Then, prescriptions were evaluated by an independent committee of ART prescribers. One hundred and thirty two consecutive initial prescriptions by 34 physicians of 11 medical centers were included: 71 M, migrants: 57 %, MSM: 21 %, CD4100 000 cp/mL (33 %). cART regimen were: NRTI/PI (43 %), NRTI/NNRTI (29.5 %), NRTI/integrase inhibitor (23 %). 75 % of initial cART regimen were consistent with expert guidelines recommendations. The choice of initial cART was not influenced by the type of HIV contamination risk group, patient's geographic origin, CD4 levels. In contrast, working or not (P=0.007), pregnancy wish (P=0.07), pregnancy (P=0.001), HIV RNA levels (P=0.02) and HIV primary infection (P=0.049) influenced the initial choice. Neither physician's age, nor physician's experience influenced this choice. The prescription's non accordance to 2013 French guidelines was mainly related to integrase inhibitor utilisation (P= 0.0001). Overall, cART initial choice is mostly consistent with guidelines. Primary HIV infection, procreation features and high viral load are the main factors influencing this choice. New regimen with better tolerability is prescribed even if it is not yet included in the guidelines. Copyright © 2016 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  12. Medications Used in Evidence-Based Regimens for Medical Abortion: An Overview.

    Science.gov (United States)

    Soon, Judith A; Costescu, Dustin; Guilbert, Edith

    2016-07-01

    Abortion is one of the most common medical procedures a woman experiences in her lifetime. Even though overall rates of abortion are decreasing slightly, medical abortion rates are expected to increase in Canada following approval by Health Canada of a combination of mifepristone and misoprostol for use in medical abortion. We conducted a literature review as part of the development of the 2016 Society of Obstetricians and Gynaecologists of Canada's Clinical Practice Guidelines on medical abortion. We searched the PubMed, MEDLINE, and Cochrane databases for articles published between 1986 and 2015 using the MeSH terms "induced abortion," "medical abortion," "mifepristone," "misoprostol," "methotrexate," and "prostaglandin." Additionally, we reviewed existing international medical abortion guidelines and searched reference lists. The most commonly studied medical abortion regimens are combinations of mifepristone and misoprostol, methotrexate and misoprostol, mifepristone and prostaglandin, and misoprostol only. Each of these regimens is a potential therapeutic choice; the advantages and disadvantages of each regimen are discussed. Drugs used for medical abortion are safe; however, clinicians who provide medical abortion and those who provide care to women who have undergone medical abortion should have an understanding of the pharmacokinetics and clinical effects of the medications used to improve outcomes and mitigate risk. Copyright © 2016 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. All rights reserved.

  13. Genital lesions: An indication for changing ART regimen.

    Science.gov (United States)

    Kumar, S Arun; Kumar, N; Kumarasamy, N

    2011-01-01

    Genital lesions are common in HIV positive patients and aetiology for these are mainly due to HSV, HPV or bacterial. They usually respond to HAART, antiviral or antimicrobials. We are presenting a young patient on HAART with non-healing genital ulcer lesions for sixteen months. He responded well to a change in ART regimen within a period of 15 days. This happened after a change to a more potent ART regimen.

  14. Baseline resistance and virological outcome in patients with virological failure who start a regimen containing abacavir: EuroSIDA study

    NARCIS (Netherlands)

    Cabrera, Cecilia; Cozzi-Lepri, Alessandro; Phillips, Andrew N.; Loveday, Clive; Kirk, Ole; Ait-Khaled, Mounir; Reiss, Peter; Kjaer, Jesper; Ledergerber, Bruno; Lundgren, Jens D.; Clotet, Bonaventura; Ruiz, Lidia

    2004-01-01

    Objectives: To investigate the ability of several HIV-1 drug-resistance interpretation systems, as well as the number of pre-specified combinations of abacavir-related mutations, to predict virological response to abacavir-containing regimens in antiretroviral therapy-experienced, abacavir-naive

  15. Clinical pharmacokinetics and pharmacodynamics of dolutegravir used as a single tablet regimen for the treatment of HIV-1 infection

    NARCIS (Netherlands)

    Bollen, Pauline; Reiss, Peter; Schapiro, Jonathan; Burger, David

    2015-01-01

    With the introduction of the coformulated dolutegravir, abacavir and lamivudine , a new single tablet regimen (STR) is made available for the use in treatment-naive and treatment-experienced HIV-infected patients. This drug combination is the fourth STR that will be positioned next to the STRs with

  16. Clinical pharmacokinetics and pharmacodynamics of dolutegravir used as a single tablet regimen for the treatment of HIV-1 infection

    NARCIS (Netherlands)

    Bollen, P.; Reiss, P.; Schapiro, J.; Burger, D.M.

    2015-01-01

    INTRODUCTION: With the introduction of the coformulated dolutegravir, abacavir and lamivudine , a new single tablet regimen (STR) is made available for the use in treatment-naive and treatment-experienced HIV-infected patients. This drug combination is the fourth STR that will be positioned next to

  17. Reasons and Risk Factors for the Initial Regimen Modification in Chinese Treatment-Naive Patients with HIV Infection: A Retrospective Cohort Analysis.

    Directory of Open Access Journals (Sweden)

    Jianjun Sun

    Full Text Available To investigate the reasons and risk factors for modification of the first combined antiretroviral therapy (cART currently used for HIV infected patients who were treatment naïve in Shanghai China.Making a retrospective observational research on treatment naïve patients with HIV infection who initiated cART during the period of September 1st 2005---December 1st 2013. The demographic and clinical data were collected from the first visit to the time of the first regimen modification or the last visit in December 1st, 2014. The reasons of treatment modification were recorded. Survival analysis of modification was made by Kaplan-Meier curves analysis and log rank test, and a Cox multiple regression model was constructed to identify related factors of modification.A total number of the eligible participants were 3372 and 871(25.8% patients changed their first cART regimen. The median follow up was 22 months [interquartile range (IQR 14-39]. Among patients who modified the original regimen, drug toxicity occurred in 805(92.4% participants and 44(5.1% experienced treatment failure. In multiple regression analysis regimen modification was associated with patients' age more than 40 years old (aHR 1.224, 95%CI 1.051-1.426, P = 0.010, CD4 less than 200(aHR 1.218, 95%CI 1.044-1.421, P = 0.012 and the initial regimen they received. Compared with the regimen of TDF+3TC+EFV, patients with regimen of d4T+3TC+NVP, d4T+3TC+EFV, AZT+3TC+NVP or AZT+3TC+EFV were 10.4, 8.2, 6.4, 2.5 times more likely to modify their initial regimen, respectively.The main reason for the regimen switch was drug toxicity and main risk factors for regimen modification were age older than 40 years, CD4 cell counts less than 200 at baseline and regimen they received. Among the 2NRTI plus 1NNRTI regimens, the co-formulation of d4T+3TC+NVP had the highest risk for modification while the regimen of TDF+3TC+EFV was the most tolerable treatment regimen in first years' follow up.

  18. Hypofractionation Regimens for Stereotactic Radiotherapy for Large Brain Tumors

    International Nuclear Information System (INIS)

    Yuan Jiankui; Wang, Jian Z.; Lo, Simon; Grecula, John C.; Ammirati, Mario; Montebello, Joseph F.; Zhang Hualin; Gupta, Nilendu; Yuh, William T.C.; Mayr, Nina A.

    2008-01-01

    Purpose: To investigate equivalent regimens for hypofractionated stereotactic radiotherapy (HSRT) for brain tumor treatment and to provide dose-escalation guidance to maximize the tumor control within the normal brain tolerance. Methods and Materials: The linear-quadratic model, including the effect of nonuniform dose distributions, was used to evaluate the HSRT regimens. The α/β ratio was estimated using the Gammaknife stereotactic radiosurgery (GKSRS) and whole-brain radiotherapy experience for large brain tumors. The HSRT regimens were derived using two methods: (1) an equivalent tumor control approach, which matches the whole-brain radiotherapy experience for many fractions and merges it with the GKSRS data for few fractions; and (2) a normal-tissue tolerance approach, which takes advantages of the dose conformity and fractionation of HSRT to approach the maximal dose tolerance of the normal brain. Results: A plausible α/β ratio of 12 Gy for brain tumor and a volume parameter n of 0.23 for normal brain were derived from the GKSRS and whole-brain radiotherapy data. The HSRT prescription regimens for the isoeffect of tumor irradiation were calculated. The normal-brain equivalent uniform dose decreased as the number of fractions increased, because of the advantage of fractionation. The regimens for potential dose escalation of HSRT within the limits of normal-brain tolerance were derived. Conclusions: The designed hypofractionated regimens could be used as a preliminary guide for HSRT dose prescription for large brain tumors to mimic the GKSRS experience and for dose escalation trials. Clinical studies are necessary to further tune the model parameters and validate these regimens

  19. Novel Combination Chemotherapy for Localized Ewing Sarcoma

    Science.gov (United States)

    In this clinical trial, researchers will test whether the addition of the drug combination vincristine, topotecan, and cyclophosphamide to a standard chemotherapy regimen improves overall survival in patients with extracranial Ewing

  20. The mortality and response rate after FLANG regimen in patients with refractory/relapsed acute leukemia

    Directory of Open Access Journals (Sweden)

    Vali A Mehrzad

    2012-01-01

    Full Text Available Background: Oncologists today are greatly concerned about the treatment of relapsed/refractory acute leukemia. FLANG regimen, combination of novantron, cytarabine, fludarabine, and granulocyte-colony stimulating factor, has been used in treatment of refractory/relapsed acute leukemia since 1990s. The present study has evaluated mortality and response rate of this regimen. Materials and Methods: In this study, 25 patients with refractory/relapsed acute leukemia aged 15-55 years underwent FLANG regimen at Seyed-Al-Shohada Hospital, Isfahan, Iran during 2008-2009. One month later, bone marrow samples were taken to evaluate the responsiveness to treatment. Participants were followed for a year. The data was analyzed by student-t and chi-square tests, logistic, and Cox regression analysis, and Kaplan-Meier curves in SPSS 19. Results: Out of the 25 patients, 8 patients (32% had acute lymphoblastic leukemia (5 refractory and 3 relapsed cases and 17 subjects had acute myeloid leukemia (7 refractory and 10 relapsed cases. According to the bone marrow biopsies taken one month after FLANG regimen, 10 patients (40% had responded to treatment. Five patients of the 10 responders underwent successful bone marrow transplantation (BMT. On the other hand, 13 patients (52%, who had not entered the CR period, died during the follow-up. Logistic regression analysis did not reveal any significant associations between disease type and responsiveness to treatment. Conclusion: This study indicated higher rates of unresponsiveness to treatment while its mortality rate was comparable with other studies. Overall, according to limitations for BMT (as the only chance for cure in Iran, it seems that FLANG therapy is an acceptable choice for these patients.

  1. The influence of patient beliefs and treatment satisfaction on the discontinuation of current first-line antiretroviral regimens.

    Science.gov (United States)

    Casado, J L; Marín, A; Romero, V; Bañón, S; Moreno, A; Perez-Elías, M J; Moreno, S; Rodriguez-Sagrado, M A

    2016-01-01

    Large cohort studies have shown a high rate of first-line combination antiretroviral therapy (cART) regimen discontinuation in HIV-infected patients, attributed to characteristics of the cART regimen or toxicity. A cohort study of 274 patients receiving a first-line regimen was carried out. Patients' perceptions and beliefs prior to initiation were assessed using an attitude towards medication scale (0-15 points), and their satisfaction during therapy was assessed using an HIV treatment satisfaction questionnaire (HIVTSQ). Treatment discontinuation was defined as any switch in the cART regimen. During 474.8 person-years of follow-up, 63 (23%) patients changed their cART regimen, mainly because of toxicity/intolerance (42; 67%). The overall rate of change was 13.2 per 100 patient-years [95% confidence interval (CI) 11.1-16.4 per 100 patient-years]. An efavirenz (EFV)-based single tablet regimen showed the highest rate of adverse events (27%), but the lowest rate of change (16%; 7.44 per 100 patient-years). Cox regression revealed a decreased hazard of first regimen termination with better initial attitude towards drugs [hazard ratio (HR) 0.76; 95% CI 0.62-0.93; P satisfaction (HR 0.94; 95% CI 0.89-0.99; P = 0.01), and an increased hazard of termination with the presence of adverse events (HR 7.7; 95% CI 2.4-11.6; P patients (18 of 59; 31%) with mild/moderate adverse events (which were mainly central nervous system symptoms) continued the regimen; these patients, compared with those discontinuing therapy, showed better perception of therapy (mean score 14.4 versus 12.1, respectively; P = 0.05) and greater satisfaction during therapy (mean score 50.6 versus 44.6, respectively; P = 0.04). Patients' beliefs and satisfaction with therapy influence the durability of the first antiretroviral regimen. These patient-related factors modulate the impact of mild adverse events, and could explain differences in the rate of discontinuation. © 2015 British HIV

  2. Abstractive Summarization of Drug Dosage Regimens for Supporting Drug Comparison.

    Science.gov (United States)

    Ugon, Adrien; Berthelot, Hélène; Venot, Alain; Favre, Madeleine; Duclos, Catherine; Lamy, Jean-Baptiste

    2015-01-01

    Complicated dosage regimens often reduce adherence to drug treatments. The ease-of-administration must thus be taken into account when prescribing. Given one drug, there exists often several dosage regimens. Hence, comparison to similar drugs is difficult. Simplifying and summarizing them appears to be a required task for supporting General Practitioners to find the drug with the simplest regimen for the patient. We propose a summarization in two steps: first prunes out all low-importance information, and second proceed to fusion of remaining information. Rules for pruning and fusion strategies were designed by an expert in drug models. Evaluation was conducted on a dataset of 169 drugs. The agreement rate was 27.2%. We demonstrate that applying rules leads to a result that is correct by a computational point of view, but the result is often meaningless for the GP. We conclude with recommendations for further work.

  3. Utilization and evaluation of noncore chemotherapy regimens within an academic medical center.

    Science.gov (United States)

    Jared, Jason R; Mably, Mary S; Makielski, Rory; Reed, Michael P; Fallon, Michael J; Liu, Glenn; Mulkerin, Daniel; Callander, Natalie S

    2017-10-01

    Uniformity of evidence-based chemotherapy prescribing using approved, standard, or "core" regimens provides systems-based safety. Noncore chemotherapy regimens are non-standard-of-care regimens requested by physicians on a patient-by-patient basis. Chemotherapy Council, a Pharmacy & Therapeutics subcommittee, assesses all requests and determines approval status based upon submitted evidence and patient-specific factors. This study's purpose is to describe noncore chemotherapy regimens utilization, efficacy, and clinical outcomes in patients receiving noncore chemotherapy regimens. This retrospective chart review includes a two-stage utilization and outcomes evaluation of patients receiving noncore chemotherapy regimens. Stage I, a demographics and utilization assessment of patients receiving noncore chemotherapy regimens, has data collection including patient age, sex, performance score, malignancy, and noncore chemotherapy regimen use justification. Stage II assesses noncore chemotherapy regimen-related, patient-specific outcomes of breast cancer noncore chemotherapy regimen patients. Breast cancer patients were evaluated on regimen and clinical outcomes including disease stage, regimen duration, discontinuation reason, subsequent chemotherapy, survival, and time from noncore chemotherapy regimen until death. Within stage I, 307 patient-specific noncore chemotherapy regimen requests were submitted. The most commonly submitted rationale was modification of a core regimen (33%), followed by patient-specific factors (29%) and salvage therapy (22%). For stage II, 29 breast cancer patients received a noncore chemotherapy regimen and most (54%) received a modified core regimen. The vast majority of noncore chemotherapy regimen discontinuation was due to either regimen completion (42%) or disease progression (42%). Nonelective hospitalizations (35%) and mortality (30%) were found during the median 13.3 months of follow up. Noncore chemotherapy regimen use provides

  4. Characteristics of HIV antiretroviral regimen and treatment adherence

    Directory of Open Access Journals (Sweden)

    Vera Lúcia da Silveira

    Full Text Available The relationship between characteristics of HIV antiretroviral regimens and treatment adherence was studied in adolescent and adult patients who underwent antiretroviral therapy from January 1998 to September 2000, at the Service for Specialized Assistance in Pelotas. The patients were interviewed on two occasions, and the use of antiretrovirals during the previous 48 hours was investigated by a self-report. Adherence was defined as use of 95% or more of the prescribed medication. Social-demographic variables were collected through direct questionnaires. The antiretroviral regimen and clinical data were copied from the patients' records. Associations between the independent variables and adherence were analyzed by means of logistic regression. The multivariate analysis included characteristics of the antiretroviral regimens, social-demographic variables, as well as perception of negative effects, negative physiological states, and adverse effects of the treatment. Among the 224 selected patients, 194 participated in our study. Their ages varied from 17 to 67 years; most patients were men, with few years of schooling and a low family income. Only 49% adhered to the treatment. Adherence to treatment regimens was reduced when more daily doses were indicated: three to four doses (odds ratio of adherence to treatment (OR=0.47, 95% confidence interval (CI 0.22-1.01 and five to six (OR=0.24, 95% CI 0.09-0.62; two or more doses taken in a fasting state (OR=0.59, 95% CI 0.11-0.68, and for patients who reported adverse effects to the treatment (OR=0.39, 95% CI 0.19-0.77. Most of the regimens with more than two daily doses of medication included at least one dose apart from mealtimes. The results suggest that, if possible, regimens with a reduced number of doses should be chosen, with no compulsory fasting, and with few adverse effects. Strategies to minimize these effects should be discussed with the patients.

  5. The Impact and Cost-Effectiveness of a Four-Month Regimen for First-Line Treatment of Active Tuberculosis in South Africa.

    Science.gov (United States)

    Knight, Gwenan M; Gomez, Gabriela B; Dodd, Peter J; Dowdy, David; Zwerling, Alice; Wells, William A; Cobelens, Frank; Vassall, Anna; White, Richard G

    2015-01-01

    A 4-month first-line treatment regimen for tuberculosis disease (TB) is expected to have a direct impact on patient outcomes and societal costs, as well as an indirect impact on Mycobacterium tuberculosis transmission. We aimed to estimate this combined impact in a high TB-burden country: South Africa. An individual based M. tb transmission model was fitted to the TB burden of South Africa using a standard TB natural history framework. We measured the impact on TB burden from 2015-2035 of introduction of a non-inferior 4-month regimen replacing the standard 6-month regimen as first-line therapy. Impact was measured with respect to three separate baselines (Guidelines, Policy and Current), reflecting differences in adherence to TB and HIV treatment guidelines. Further scenario analyses considered the variation in treatment-related parameters and resistance levels. Impact was measured in terms of differences in TB burden and Disability Adjusted Life Years (DALYs) averted. We also examined the highest cost at which the new regimen would be cost-effective for several willingness-to-pay thresholds. It was estimated that a 4-month regimen would avert less than 1% of the predicted 6 million person years with TB disease in South Africa between 2015 and 2035. A similarly small impact was seen on deaths and DALYs averted. Despite this small impact, with the health systems and patient cost savings from regimen shortening, the 4-month regimen could be cost-effective at $436 [NA, 5983] (mean [range]) per month at a willingness-to-pay threshold of one GDP per capita ($6,618). The introduction of a non-inferior 4-month first-line TB regimen into South Africa would have little impact on the TB burden. However, under several scenarios, it is likely that the averted societal costs would make such a regimen cost-effective in South Africa.

  6. What to Start: Selecting a First HIV Regimen

    Science.gov (United States)

    ... CCR5 antagonists Integrase strand transfer inhibitors (INSTIs) Post-attachment inhibitors In general, a person's first HIV regimen includes two NRTIs plus an INSTI, an NNRTI, or a PI boosted with cobicistat (brand name: Tybost) or ritonavir (brand name: Norvir). Cobicistat ...

  7. Assessment of non-standard HIV antiretroviral therapy regimens at ...

    African Journals Online (AJOL)

    2016-03-06

    Mar 6, 2016 ... Aim. Lighthouse Trust in Lilongwe, Malawi serves approximately 25,000 patients with HIV antiretroviral therapy (ART) regimens standardized according to national treatment guidelines. However, as a referral centre for complex cases, Lighthouse Trust occasionally treats patients with non-standard ART.

  8. Effects of different penning conditions, feeding regimens and season ...

    African Journals Online (AJOL)

    The pigs were randomly allocated to three feeding regimens, a controlled single feeding, ad libitum single feeding and ad libitum group feeding, with six animals per ad libitum group. This resulted in 96 pigs in six treatments with six replicates. The diets were high (HF) and low (LF) nutrient dense feeds, where the LF was ...

  9. Comparison of different insulin regimens in elderly patients with NIDDM

    NARCIS (Netherlands)

    Wolffenbuttel, B H; Sels, J P; Rondas-Colbers, G J; Menheere, P P; Nieuwenhuijzen Kruseman, A C

    1996-01-01

    OBJECTIVE: To compare the metabolic effects of three different frequently used regimens of insulin administration on blood glucose control and serum lipids, and the costs associated with this treatment, in subjects with NIDDM, who were poorly controlled with oral antihyperglycemic agents. RESEARCH

  10. Randomization of two dosing regimens of vaginal misoprostol for ...

    African Journals Online (AJOL)

    Objectives: To compare the effectiveness of two dosing regimens of vaginal misoprostol for cervical ripening and induction of labour. Materials and Methods: Pregnant women with singleton low risk pregnancy at term scheduled for elective induction of labour were randomized to receive either 25 µg or 50 µg of vaginal ...

  11. The liberal peace security regimen: a gramscian critique of its ...

    African Journals Online (AJOL)

    Current security regimens are grounded in the advancement of liberal peace. All inter-governmental organizations, most states and most donor agencies more or less accept as common sense the self-evident virtuosity and truth of the liberal peace project. However, there is a profound contradiction within this project in ...

  12. mtct regimen choice, drug resistance and the treatment of hiv

    African Journals Online (AJOL)

    drug-resistant variants may become selected as long as the drug is administered. There has been some concern that the use of ARV monotherapy for the prevention of MTCT, including ... potential implications for perinatal transmission, the choice of ... transmission rate using this regimen, short-term treatment with dual ...

  13. Assessment of non-standard HIV antiretroviral therapy regimens at ...

    African Journals Online (AJOL)

    2016-03-06

    Mar 6, 2016 ... guidelines for children and not adults. Discussion. Less than 1% of the 17,000 patients receiving ART for treatment of HIV at Lighthouse Trust in 2012 were being treated with NS-ART, signifying a strong adherence to standardized regimens by clinicians. Assessing the reasons for use of NS-ART is essential ...

  14. outcome and haemato-toxicity of two chemotherapy regimens for ...

    African Journals Online (AJOL)

    2009-12-02

    Dec 2, 2009 ... enhancement of bone marrow toxicity and inability to provide necessary .... Consolidation (2 courses 7-10 days apart). - adriamycin ... study cases. Follow up period ranged between one and 18 months with a median of seven months from time of diagnosis. In the short course regimen, 58.3% presented with ...

  15. mtct regimen choice, drug resistance and the treatment of hiv

    African Journals Online (AJOL)

    Perinauzl HW Unit, University ofcJu WilWalmTand. MTCT REGIMEN CHOICE, DRUG. RESISTANCE AND THE TREATMENT OF. HIV-I-INFECTED CHILDREN assessing ARV drug resistance. Genotypic assays detect specific point mutations in the HIV genome that are associated with phenotypic resistance. These are most.

  16. Gonzalez Regimen (PDQ®)—Health Professional Version

    Science.gov (United States)

    The Gonzalez regimen is a specialized diet that uses enzymes, supplements, and other factors in cancer management. It is based on a theory that involves the use of pancreatic enzymes to help the body get rid of toxins that lead to cancer. Read about existing clinical data in this expert-reviewed summary.

  17. A network meta-analysis of eight chemotherapy regimens for treatment of advanced ovarian cancer.

    Science.gov (United States)

    Jiang, Xi-Ping; Rui, Xiao-Hui; Guo, Cai-Xia; Huang, Ya-Qing; Li, Qin; Xu, Yun

    2017-03-21

    This study compared the short-term efficacies of different chemotherapy regimens in the treatment of advanced ovarian cancer (AOC) through pair-wise and network meta-analyses (NMA). Randomized controlled trials (RCTs) identified in a comprehensive online literature search met our inclusion criteria. Direct and indirect evidence was combined to compare odds ratios (OR) and surfaces under the cumulative ranking curves (SUCRA) across the different treatment regimens. Twelve eligible RCTs were finally included, involving eight regimens (Paclitaxel + Carboplatin [PC], Gemcitabine + Carboplatin [GC], Carboplatin, Pegylated Liposomal Doxorubicin + Carboplatin [PLD + Carboplatin], Paclitaxel, Paclitaxel + Carboplatin + Topotecan [PC + Topotecan], Paclitaxel + Carboplatin + Epirubicin [PC + Epirubicin] and Docetaxel + Carboplatin [DC]). The NMA results revealed that in terms of overall response rate (ORR) and disease control rate (DCR), PC (ORR: OR=2.59, 95%CI=1.20-6.22; DCR: OR=2.58, 95%CI=1.05-6.82) and GC (ORR: OR=2.08, 95%CI=1.08-4.37; DCR: OR=2.43, 95%CI=1.07-5.80) were more effective against AOC than Carboplatin alone. Similarly, PC (OR=0.21, 95%CI=0.05-0.69), GC (OR=0.31, 95%CI=0.09-0.90) and PLD + Carboplatin (OR=0.22, 95%CI=0.04-0.92) slowed disease progression better than Carboplatin alone. We also found that PC was more efficacious against AOC than Carboplatin or Paclitaxel single-agent chemotherapy. Combination chemotherapy is thus recommended for AOC, and should guide subsequent drug development and treatment strategies.

  18. [Efficacy of NO regimen and NP regimen on advanced non-small cell lung cancer: a prospective randomized trial].

    Science.gov (United States)

    Gao, Jian-Fei; Zhang, Xin-Hua; Wang, Jun; Rao, Zhi-Guo; Zhu, Yu-Ze; Ou, Wu-Ling; Zhang, Bi-Cheng; Du, Guang-Zu

    2005-08-01

    Oxaliplatin (LOHP) is an effective drug in treatment of non-small cell lung cancer (NSCLC) with mild toxicities to gastrointestinal tract, kidney, and bone marrow. Cisplatin (DDP) plus vinorelbine (NVB) constitute the first-line regimen (NP regimen) for NSCLC. This study was to compare the short-term response, long-term outcome, and adverse events between advanced NSCLC patients received NO regimen (LOHP plus NVB) and NP regimen. A total of 90 patients with advanced NSCLC were randomized into NO group (58 patients, 25 mg/m(2) of NVB, day 1 and day 8; 130 mg/m(2) of LOHP, day 1) and NP group (32 patients, 25 mg/m(2) of NVB, day 1 and day 8; 50 mg/m(2) of DDP, day 2 and day 3). The short-term response, long-term outcome, adverse events, and survival status of the 2 groups were observed. The response rates were 33.33% in NO group, and 35.48% in NP group, but no significant difference was detected between the 2 groups (P > 0.05). The clinical benefit response rate was significantly higher in NO group than in NP group (80.70% vs. 64.52%, P NP group; the median time of remission was 21 weeks in NO group, and 19 weeks in NP group; the median survival time was 39 weeks in NO group, and 37 weeks in NP group; the 1-year survival rate was 37.93% in NO group, and 31.25% in NP group. No significant differences were detected between the 2 groups. The incidence rates of phlebitis and grade I-II peripheral neuritis were significantly higher in NO group than in NP group (77.59% vs. 50.00%, Pvs. 15.63%, PNP group than in NO group (31.25% vs. 3.45%, PNP regimen, but the clinical benefit response rate is higher in NO group than in NP group. In short, NO regimen may be recommended as the first-line chemotherapy regimen for advanced NSCLC.

  19. Sedation analgesia during office-based plastic surgery procedures: comparison of two opioid regimens.

    Science.gov (United States)

    Cinnella, Gilda; Meola, Salvatore; Portincasa, Aurelio; Parisi, Domenico; Morgese, Francesco; Pavone, Giovanna; Dambrosio, Michele

    2007-06-01

    The combination of sedative and analgesic drugs is increasingly being used during minimally invasive surgery. The authors compared the clinical efficacy of two different fentanyl regimens, in combination with midazolam, for sedation analgesia in patients undergoing office-based plastic surgery procedures under local anesthesia. One-hundred patients were randomized into two groups of 50 subjects each. Group F1 received a fentanyl bolus of 0.7 microg/kg before infiltration with local anaesthetics; group F2 received the same bolus plus 0.6 microg/kg fentanyl every 45 minutes. All patients received a midazolam bolus of 0.05 mg/kg plus continuous infusion 0.08 mg/kg per hour. High-quality analgesia was obtained in every group, without significant differences between the two fentanyl regimens. Group F2 was associated with lower intraoperative mean blood pressure and SpO2 values compared with group F1. No differences were detected between the two groups in perioperative side effects or postoperative pain. Higher doses of opioid did not improve the quality of perioperative patient comfort but acted synergistically with the sedative drugs, amplifying the hemodynamic and respiratory side effects.

  20. NOVP: a novel chemotherapeutic regimen with minimal toxicity for treatment of Hodgkin's disease

    Energy Technology Data Exchange (ETDEWEB)

    Hagemeister, F.B.; Cabanillas, F.; Velasquez, W.S.; Meistrich, M.L.; Liang, J.C.; McLaughlin, P.; Redman, J.R.; Romaguera, J.E.; Rodriguez, M.A.; Swan, F. Jr. (Univ. of Texas, M.D. Anderson Cancer Center, Houston (USA))

    1990-12-01

    Patients with early-staged Hodgkin's disease have had a higher relapse rate following radiotherapy alone if they have B symptoms, large mediastinal masses, hilar involvement, or stage III disease. From June 1988 to December 1989, 27 previously untreated patients with early-staged Hodgkin's disease with adverse features for disease-free survival received combined-modality therapy. Seventeen patients had stage I or II disease, 10 had stage III, 5 had B symptoms, 13 had large mediastinal masses, and 6 had peripheral masses measuring 10 cm or more in diameter. All patients initially received three cycles of a novel chemotherapeutic regimen combining Novantrone (mitoxantrone, American Cyanamid Company), vincristine, vinblastine, and prednisone (NOVP). Twenty-four patients with clinically staged I or II disease with adverse features or stage III disease did not undergo laparotomy; three patients had favorable stage I or II disease and at laparotomy had stage III disease. Radiotherapy-treatment fields depended on the extent of nodal involvement. Twenty-six patients completed all therapy as planned to complete remission (CR) and one of these has had progression; she is in second CR following additional radiotherapy. With a median follow-up of 12 months, all patients are alive. Tolerance to treatment was excellent with only grade 1 or 2 nausea, alopecia and myalgias, and brief myelosuppression. NOVP is an effective adjuvant chemotherapy regimen for inducing responses, with minimal toxicity, prior to definitive radiotherapy for patients with early-staged Hodgkin's disease.

  1. Single-tablet regimens in HIV: does it really make a difference?

    Science.gov (United States)

    Aldir, Isabel; Horta, Ana; Serrado, Margarida

    2014-01-01

    Review of the available data on the currently available single-tablet regimens (STRs), from the analysis of efficacy and safety to the key points of value in terms of adherence, quality of life and pharmacoeconomic evaluation. For this narrative review, literature searches have been performed in PubMed, IndexRevMed and Cochrane, using the search terms HIV, single-tablet, one-pill, single dose, fixed-dose, and STR. These have been reviewed and complemented with the most recent publications of interest. Fixed-dose combinations are a significant advance in antiretroviral treatment simplification, contributing to an increase in compliance with complex chronic therapies, thus improving patients' quality of life. Reducing the number of pills and daily doses is associated with higher adherence and better quality of life. As a fixed-dose combination tablet given once daily, EFV/FTC/TDF was the first available STR combining efficacy, tolerability and convenience, with the simplest dosing schedule and smallest numbers of pills of any ART combination therapy. The RPV/FTC/TDF is a next-generation NNRTI-based STR, a once daily complete ART regimen for the treatment of HIV-1 infection. Recently the combination of EVG/COBI/FTC/TDF was also approved by the European Commission, and is the first integrase inhibitor-based STR. Receiving antiretroviral therapy as once daily STR is associated with both clinical and economic benefits, which confirms previous research. The associated benefits of STRs provide a valid strategy for the treatment of HIV-infected patients.

  2. Cost/efficacy analysis of preferred Spanish AIDS study group regimens and the dual therapy with lopinavir/ritonavir plus lamivudine for initial ART in HIV infected adults.

    Science.gov (United States)

    Gatell Artigas, Josep María; Arribas López, José Ramón; Lázaro Y de Mercado, Pablo; Blasco Bravo, Antonio Javier

    2016-01-01

    The National AIDS Plan and the Spanish AIDS study group (GESIDA) proposes "preferred regimens" (PR) of antiretroviral treatment (ART) as initial therapy in HIV-infected patients. In 2013, the recommended regimens were all triple therapy regimens. The Gardel Study assessed the efficacy of a dual therapy (DT) combination of lopinavir/ritonavir (LPV/r) plus lamivudine (3TC). Our objective is to evaluate the GESIDA PR and the DT regimen LPV/r+3TC cost/efficacy ratios. Decision tree models were built. probability of having viral load <50 copies/mL at week 48. ART regime cost: costs of ART, adverse effects, and drug resistance tests during the first 48 weeks. Cost/efficacy ratios varied between 5,817 and 13,930 euros per responder at 48 weeks, for the DT of LPV/r+3TC and tenofovir DF/emtricitabine+raltegravir, respectively. Taking into account the official Spanish prices of ART, the most efficient regimen was DT of LPV/r+3TC, followed by the triple therapy with non-nucleoside containing regimens. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  3. Effect of 21-day and 24-day oral contraceptive regimens containing gestodene (60 microg) and ethinyl estradiol (15 microg) on ovarian activity.

    Science.gov (United States)

    Sullivan, H; Furniss, H; Spona, J; Elstein, M

    1999-07-01

    To compare ovulation inhibition and ovarian activity with 21-day and 24-day regimens of a low-dose combined oral contraceptive (COC) containing 60 microg of gestodene and 15 microg of ethinyl estradiol. Interventional observational study. Reproductive medicine unit. Fifty-eight healthy volunteers aged 18-35 years. Ovarian activity was monitored every other day with the use of ultrasound to measure the diameters of follicle-like structures and blood samples to measure serum concentrations of 17beta-E2 and progesterone. Subjects were observed for five cycles: pretreatment and posttreatment control cycles and three cycles in which the COC was administered for either 21 or 24 days of each cycle. Occurrence of ovulation and evidence of ovarian activity. The study was completed by 27 (90%) of the 30 subjects who received the 24-day regimen and by 24 (79%) of the 28 subjects who received the 21-day regimen. Ovulation was inhibited in all cycles in the 24-day group and in 74 of 75 cycles in the 21-day group. Luteinized unruptured follicles were seen in no cycles with the 24-day regimen and in 6 (8%) of 75 cycles with the 21-day regimen. Mean ovarian follicular development and serum 17beta-E2 and progesterone levels were lower in the 24-day group. The 24-day regimen is an innovative strategy for maintaining effective ovulation inhibition at ultra-low doses of contraceptive steroids.

  4. A Faropenem, Linezolid, and Moxifloxacin Regimen for Both Drug-Susceptible and Multidrug-Resistant Tuberculosis in Children: FLAME Path on the Milky Way.

    Science.gov (United States)

    Deshpande, Devyani; Srivastava, Shashikant; Nuermberger, Eric; Pasipanodya, Jotam G; Swaminathan, Soumya; Gumbo, Tawanda

    2016-11-01

     The regimen of linezolid and moxifloxacin was found to be efficacious in the hollow fiber system model of pediatric intracellular tuberculosis. However, its kill rate was slower than the standard 3-drug regimen of isoniazid, rifampin, and pyrazinamide. We wanted to examine the effect of adding a third oral agent, faropenem, to this dual combination.  We performed a series of studies in the hollow fiber system model of intracellular Mycobacterium tuberculosis, by mimicking pediatric pharmacokinetics of each antibiotic. First, we varied the percentage of time that faropenem persisted above minimum inhibitory concentration (T MIC ) on the moxifloxacin-linezolid regimen. After choosing the best faropenem exposure, we performed experiments in which we varied the moxifloxacin and linezolid doses in the triple regimen. Finally, we performed longer-duration therapy validation experiments. Bacterial burden was quantified using both colony-forming units per milliliter (CFU/mL) and time to positivity (TTP). Kill slopes were modeled using exponential regression.  TTP was a more sensitive measure of bacterial burden than CFU/mL. A faropenem T MIC > 62% was associated with steepest microbial kill slope. Regimens of standard linezolid and moxifloxacin plus faropenem T MIC > 60%, as well as higher-dose moxifloxacin, achieved slopes equivalent to those of the standard regimen based by both TTP and CFU/mL over 28 days of treatment.  We have developed an oral faropenem-linezolid-moxifloxacin (FLAME) regimen that is free of first-line drugs. The regimen could be effective against both multidrug-resistant and drug-susceptible tuberculosis in children. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  5. Noncompliance with Medical Regimen in Haemodialysis Treatment: A Case Study

    Directory of Open Access Journals (Sweden)

    Paraskevi Theofilou

    2011-01-01

    Full Text Available Patients undergoing haemodialysis treatment have a high burden of disease (particularly cardiovascular comorbidities affecting their quality of life and dramatically shortening life expectancy. Effective chronic kidney disease (CKD control requires regular preventive medication and a response to that medication. Poor receptiveness to CKD medication can be related to individual variability in the dose needed to achieve a response, as well as to low-adherent behaviour in relation to the CKD medication regimen. Some patients, though not many, according to studies' findings, abuse the medical regimen as a result of suicidal tendencies. The present case gave us the opportunity to consider the causes and clinical findings and review the specific psychological interventions for patients with CKD.

  6. INTEGRATION OF BEVACIZUMAB IN METASTATIC COLORECTAL CANCER CHEMOTHERAPY REGIMENS IN 2 CLINICAL CENTERS IN MOSCOW AND SAINT PETERSBURG

    Directory of Open Access Journals (Sweden)

    N. V. Dobrova

    2013-01-01

    Full Text Available The aim of this study was to estimate efficacy of first line chemotherapy with bevacizumab in metastatic colorectal cancer patients and investigate the impact of different prognostic factors on treatment outcome.Methods.During 2004–2008 48 colorectal cancer patients were included (29 in Russian N.N. Blokhin Cancer Research Center, 19 in St. Petersburg, who had unresectable distant metastases. Primary tumor was resected in 93.8 % patients. 52.1 % had rectal cancer. 87.5 % had liver metastases, 43.8 % had more than 1 organ affected. 66.7 % received chemotherapy with bevacizumab 5 mg/kg biweekly, 33.3 % received bevacizumab 7,5 mg/kg every 3 weeks. 62.5 % patients had oxaliplatin-based regimens, 35.4 % – only fluorpyrimidines, 2.1 % – chemotherapy with irinotecan.Results.Median time of bevacizumab use was 7.8 months. 60.3 % had objective response, 87.4 % had stable diseases during more than 6 months. Median progression-free survival (PFS was 11.5 months. Median overall survival (OS was 24.1 months.Conclusions.Survival and efficacy results are comparable to international experience. Combination of fluorpyrimidines with bevacizumab had comparable efficacy to combined chemotherapy regimens with no impact on quality of life. Integration of bevacizumab in combined treatment regimens reduced the impact of negative prognostic factors on PFS and OS. 

  7. Pilot study of a pediatric metronomic 4-drug regimen.

    Science.gov (United States)

    André, Nicolas; Abed, Sylvie; Orbach, Daniel; Alla, Corinne Armari; Padovani, Laetitia; Pasquier, Eddy; Gentet, Jean Claude; Verschuur, Arnauld

    2011-12-01

    Metronomic chemotherapy (MC) is defined as the frequent administration of chemotherapy at doses below the maximal tolerated dose and with no prolonged drug-free break. MC is gaining interest as an alternative strategy to fight resistant cancer. to assess the safety of 4 drug MC regimen in paediatric patients with refractory or relapsing various tumour types. From November 2008 to December 2010, in three academic paediatric oncology centers, 16 children (median age 12 years old; range 5.5-20) were included in this pilot study. This treatment was proposed to children with refractory disease for whom no further effective treatments were available. Most frequent diagnosis were medulloblastoma/cerebral PNET (5) osteosarcoma (5), and one case each of nephroblastoma, high grade glioma, Hodgkin lymphoma, rhabdomyosarcoma, neuroblastoma and kidney rhabdoid tumour. The MC regimen consisted in cycles of 56 days (8 weeks) with weekly vinblastine 3 mg/m2 (week 1-7), daily cyclophosphamide 30 mg/m2 (days 1-21), and twice weekly methotrexate 10 mg/m² (days 21-42), and daily celecoxib 100 mg to 400 mg twice daily (days 1-56) followed by a 2-weeks chemotherapy break. Adverse events were determined through laboratory analysis and investigator observations. One objective response was observed in a patient with Hodgkin lymphoma, and 4 patients experienced disease stabilization and continued their treatment for 3 cycles (24 weeks) or more. At last follow-up, 7 patients (43%) are alive including 1 still undergoing treatment. During the overall 36 cycles of treatments received by patients, 4 grade IV toxicities and 24 grade III toxicities were observed in 11 cycles in only 10 different patients. The metronomic regimen we report here was well tolerated and associated with disease stabilization. This regimen is currently being evaluated in a national multicenter phase II study.

  8. Predictive tools for designing new insulins and treatment regimens

    DEFF Research Database (Denmark)

    Klim, Søren

    The thesis deals with the development of "Predictive tools for designing new insulins and treatments regimens" and consists of two parts: A model based approach for bridging properties of new insulin analogues from glucose clamp experiments to meal tolerance tests (MTT) and a second part that des......The thesis deals with the development of "Predictive tools for designing new insulins and treatments regimens" and consists of two parts: A model based approach for bridging properties of new insulin analogues from glucose clamp experiments to meal tolerance tests (MTT) and a second part...... glucose profiles from a MTT with treatments based on the new insulin analogue that previously only has been tested in clamps. The bridge between insulin analogue properties determined in clamp experiments to meal tolerance test outcomes in Phase II trials is not simple and is complicated by shifts...... in experimental setup, time horizon and treatment regimen. A bridging strategy was introduced where an integrated model simulating MTTs was extended with models developed on clamp data that described PK and PD for the new insulin analogue. The bridging strategy was tested by building an integrated model based...

  9. The Hemotoxicity of Chemotherapeutic Regimens in Sudanese Children with Retinoblastoma

    Directory of Open Access Journals (Sweden)

    Fathelrahman Mahdi Hassan

    2013-01-01

    Full Text Available Background: There has been a rapid increase in cancer among Sudanese citizens from 1999 until this year. At least 80% of all patients who undergo chemotherapy will develop anemia as a complication. This inpatient analytical comparative study aims to examine the possible association between hemotoxicity and various chemotherapy regimens in Sudanese children diagnosed with retinoblastoma.Methods: This study enrolled 30 patients diagnosed with childhood retinoblastoma who were admitted from June 2006 to September 2008 to the Radiation and Isotope Center Khartoum. We collected 90 blood samples to examine for a possible association between anemia and the chemotherapeutic regimen. All patients (n=30 were included in each arm of the chemotherapy regimen.Results: Prior to the onset of chemotherapy, 50% of patients had normal hemoglobin levels, 43.3% had mild anemia, and 6.7% had moderate anemia. Post-cycle I treatment, there were only 6.7% who had normal hemoglobin levels. Mild anemia was observed in 60%, followed by 30% for moderate anemia and 3.3% of patients had severe anemia. Post-cycle II there were no patients with normal hemoglobin levels, however 26.7% had mild anemia and the majority of patients (approximately 73.3% had moderate anemia.Conclusion: A correlation existed between hemoglobin values after completion of therapy to the overall treatment. We observed a decline of 1 to 2 g/dl in hemoglobin levels.

  10. Antiretroviral regimen durability and success in treatment-naïve and treatment-experienced patients by year of treatment initiation, United States, 1996–2011

    Science.gov (United States)

    Sheth, Anandi N.; Ofotokun, Ighovwerha; Buchacz, Kate; Armon, Carl; Chmiel, Joan S.; Hart, Rachel L.D.; Baker, Rose; Brooks, John T.; Palella, Frank J.

    2015-01-01

    Background Although modern combination antiretroviral therapy (cART) regimens are better tolerated and less complex than earlier treatments, regimen modification or discontinuation remains a concern. Methods We studied HIV Outpatient Study (HOPS) participants who initiated first or second cART regimens during: 1996–1999, 2000–2003, 2004–2007 and 2008–2011. We analyzed regimen durability (time to regimen modification) and success (achieving undetectable plasma HIV RNA) for first and second cART regimens using Kaplan-Meier curves and log-rank tests, and examined factors associated with durability and success of first cART regimen using proportional hazards models. Results Durability of cART was progressively longer for cART regimens initiated in more recent periods: median first cART regimen durations were 1.0, 1.1, 2.1 and 4.6 years in 1996–1999, 2000–2003, 2004–2007 and 2008–2011, and median second cART durations were 0.9, 1.2, 2.8 and 3.9 years, respectively (both p<0.001). Comparing 1996–1999 and 2008–2011, the percentage of patients who achieved an undetectable HIV RNA within 6 months of first cART initiation increased from 65% to 81%, and from 63% to 80% on second cART (both p<0.001). Among patients initiating first cART during 2008–2011, black non-Hispanic/Latino race/ethnicity and ≥twice daily dosing were significantly associated with higher rates of regimen modification (p<0.05), and higher baseline HIV RNA levels were associated with failure to achieve an undetectable HIV RNA (p<0.001). Conclusions Among HIV-infected U.S. adults in routine HIV care, durability of first and second cART regimens and the likelihood of prompt virologic suppression increased during 1996–2011, coincident with the availability of more tolerable, less complex cART options. PMID:26334737

  11. Comparison between Efficacy of Ciprofioxacin -Doxycycline with Rifampin – Doxycycline Regimens inrelapse of Brucellosis

    Directory of Open Access Journals (Sweden)

    Hossein Sarmadian

    2014-08-01

    Full Text Available Background: Brucellosis is one of the endemic diseases in Iran that has a worldwide spread and is associated with chronic disabilities in humans. Combination therapy of Brucellosis leads to recovery of symptoms, shortening of the symptomatic intervals, and decrease in the rate of relapse and drug resistance. Considering the use of rifampin in the treatment of tuberculosis, and the necessity for an alternative treatment in regions endemic for both tuberculosis and brucellosis, the aim ofthis study was to compare the efficiency of the regimen of rifampin-Doxycycline with ciprofloxacin-Doxycycline in relapse of brucellosis. Materials and methods: This randomized controlled trial was performed on 90 patients, older than 17 years old, affected with brucellosis, which were referred to the Infectious Disease Clinics at ArakUniversity of medical sciences between the years 1384-1387. The patients were randomly divided into two groups: the DR groups, receiving 100 mg of Doxycycline twice a day and 300 mg of rifampin Bid daily for eight weeks and the CD group, receiving 100 mg of Doxycycline plus 500 mg of ciprofloxacin twice a day for eight weeks. The patients were analyzed for the relief of symptoms, drug side effects, and laboratory findings during the treatment. Results:In this study, the rate of relapse in both groups were similar. The relapse was seen in 4.5% and 3.2% of the patients for the DR and CD groups, respectively (P=0.168. The drug side effects were slight in both of groups, with no significant difference, and did not lead to discontinuation of the therapy. Conclusion: According to the same rate of relapse in both CD and DR regimens in the treatment of brucellosis and considering the usage of rifampin in regions with high prevalence of tuberclusis, the CD regimen is recommended as an appropriate one.

  12. Impact of Anesthetic Regimen on Remote Ischemic Preconditioning in the Rat Heart In Vivo

    NARCIS (Netherlands)

    Behmenburg, Friederike; van Caster, Patrick; Bunte, Sebastian; Brandenburger, Timo; Heinen, André; Hollmann, Markus W.; Huhn, Ragnar

    2017-01-01

    Remote ischemic preconditioning (RIPC) seems to be a promising cardioprotective strategy with contradictive clinical data suggesting the anesthetic regimen influencing the favorable impact of RIPC. This study aimed to investigate whether cardio protection by RIPC is abolished by anesthetic regimens.

  13. Chemotherapy for pulmonary large cell neuroendocrine carcinomas : Does the regimen matter?

    NARCIS (Netherlands)

    Derks, Jules L.; van Suylen, Robert Jan; Thunnissen, Erik; den Bakker, Michael A.; Groen, Harry J.; Smit, Egbert F.; Damhuis, Ronald A.; van den Broek, Esther C.; Speel, Ernst-Jan M.; Dingemans, Anne-Marie C.

    Pulmonary large cell neuroendocrine carcinoma (LCNEC) is rare. Chemotherapy for metastatic LCNEC ranges from small cell lung carcinoma (SCLC) regimens to nonsmall cell lung carcinoma (NSCLC) chemotherapy regimens. We analysed outcomes of chemotherapy treatments for LCNEC. The Netherlands Cancer

  14. Comparison of FOLFOX and DOF regimens as first-line treatment in East Asian patients with advanced gastric cancer

    Directory of Open Access Journals (Sweden)

    Liu M

    2018-01-01

    manageable. The combination of docetaxel/oxaliplatin/fluorouracil was active and well tolerated in AGC patients and deserves further evaluation. However, for elderly patients with AGC, the DOF regimen was associated with worse toxicities; therefore, the FOLFOX regimen might be a more suitable option. Keywords: East Asian AGC patients, chemotherapy, safety, efficacy

  15. Virological patterns of HCV patients with failure to interferon-free regimens.

    Science.gov (United States)

    Starace, Mario; Minichini, Carmine; De Pascalis, Stefania; Macera, Margherita; Occhiello, Laura; Messina, Vincenzo; Sangiovanni, Vincenzo; Adinolfi, Luigi E; Claar, Ernesto; Precone, Davide; Stornaiuolo, Gianfranca; Stanzione, Maria; Ascione, Tiziana; Caroprese, Mara; Zampino, Rosa; Parrilli, Gianpaolo; Gentile, Ivan; Brancaccio, Giuseppina; Iovinella, Vincenzo; Martini, Salvatore; Masarone, Mario; Fontanella, Luca; Masiello, Addolorata; Sagnelli, Evangelista; Punzi, Rodolfo; Salomone Megna, Angelo; Santoro, Renato; Gaeta, Giovanni B; Coppola, Nicola

    2018-05-01

    The study characterized the virological patterns and the resistance-associated substitutions (RASs) in patients with failure to IFN-free regimens enrolled in the real-life setting. All 87 consecutive HCV patients with failed IFN-free regimens, observed at the laboratory of the University of Campania, were enrolled. All patients had been treated with DAA regimens according to the HCV genotype, international guidelines, and local availability. Sanger sequencing of NS3, NS5A, and NS5B regions was performed at failure by home-made protocols. Of the 87 patients enrolled, 13 (14.9%) showed a misclassified HCV genotype, probably causing DAA failure, 16 had been treated with a sub-optimal DAA regimen, 19 with a simeprevir-based regimen and 39 with an optimal DAA regimen. A major RAS was identified more frequently in the simeprevir regimen group (68.4%) and in the optimal regimen group (74.4%) than in the sub-optimal regimen group (56.3%). The prevalence of RASs in NS3 was similar in the three groups (30.8-57.9%), that in NS5A higher in the optimal regimen group (71.8%) than in the sub-optimal regimen group (12.5%, P < 0.0001) and in the simeprevir regimen group (31.6%, P < 0.0005), and that in NS5B low in all groups (0-25%). RASs in two or more HCV regions were more frequently identified in the optimal regimen group (46.6%) than in the simeprevir-based regimen group (31.6%) and sub-optimal regimen group (18.7%). In our real-life population the prevalence of RASs was high, especially in NS3 and NS5A and in those treated with suitable DAA regimens. © 2018 Wiley Periodicals, Inc.

  16. Successful and well-tolerated bi-weekly immunoadsorption regimen in pemphigus vulgaris.

    Science.gov (United States)

    Dietze, Jenny; Hohenstein, Bernd; Tselmin, Sergey; Julius, Ulrich; Bornstein, Stefan R; Beissert, Stefan; Günther, Claudia

    2017-11-01

    Pemphigus vulgaris is a chronic autoimmune disease characterized by blisters and erosions forming in the mucous membranes and the skin. Many patients are severely impaired by pain, weight loss and increased risk of infections. The disease is mediated by specific autoantibodies directed against desmogleins that contribute to connect keratinocytes in the epidermis. Autoantibody deposition in the skin causes inflammation and intraepidermal akantholysis. The concentration of autoantibodies in serum correlates with disease activity. Therefore, the removal of autoantibodies by immunoadsorption is a targeted therapeutic intervention for patients with pemphigus vulgaris. A total of 9 patients with pemphigus vulgaris resistant to the standard treatment regimen were treated by immunoadsorption using the TheraSorb™-Ig adsorber system and analyzed retrospectively. Patients received immunoadsorption on two or four consecutive days. Cycles were repeated every two or four weeks, respectively. Treatment was performed for a mean period of 17.5 months (range 6-26). Outcome was measured as improvement in clinical disease analyzed by the investigators global assessment and the reduction of autoantibodies in serum measured by indirect immunofluorescence and ELISA. Tolerability of treatment by patients was evaluated using a visual analog scale. Retrospective analysis of 9 patients consecutively treated by immunoadsorption revealed an 80% reduction of the autoantibody concentration in serum after 6 months of treatment, led to a clinical improvement of disease in combination with classical immunosuppression. Steroid consumption could be reduced by 50% after 30 and 75% after 90 days. Therapy resulted in a total response rate of 89%, with 56% of patients reaching partial and 33% complete remission. The bi-weekly treatment regimen resulted in effective improvement of disease and was in favor to the 4-weekly regimen by the subjective judgment of tolerability by the patients

  17. Comparison of efficacy and pharmacoeconomics of two helicobacter pylori eradication regimens in peptic ulcer disease

    Directory of Open Access Journals (Sweden)

    Syeda Zaineb Kubra Hussaini

    2018-01-01

    Conclusion: Our study showed that Regimen II (RAM was more cost-effective than Regimen I (PAC, but PAC achieved faster H. pylori eradication than RAM. We assume that this study provides local clinical data as to which regimen may be useful in a particular patient. National Level Clinical Trials are required to further ascertain this conclusion.

  18. Effectiveness of multi-drug regimen chemotherapy treatment in osteosarcoma patients: a network meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Wang, Xiaojie; Zheng, Hong; Shou, Tao; Tang, Chunming; Miao, Kun; Wang, Ping

    2017-03-29

    Osteosarcoma is the most common malignant bone tumour. Due to the high metastasis rate and drug resistance of this disease, multi-drug regimens are necessary to control tumour cells at various stages of the cell cycle, eliminate local or distant micrometastases, and reduce the emergence of drug-resistant cells. Many adjuvant chemotherapy protocols have shown different efficacies and controversial results. Therefore, we classified the types of drugs used for adjuvant chemotherapy and evaluated the differences between single- and multi-drug chemotherapy regimens using network meta-analysis. We searched electronic databases, including PubMed (MEDLINE), EmBase, and the Cochrane Library, through November 2016 using the keywords "osteosarcoma", "osteogenic sarcoma", "chemotherapy", and "random*" without language restrictions. The major outcome in the present analysis was progression-free survival (PFS), and the secondary outcome was overall survival (OS). We used a random effect network meta-analysis for mixed multiple treatment comparisons. We included 23 articles assessing a total of 5742 patients in the present systematic review. The analysis of PFS indicated that the T12 protocol (including adriamycin, bleomycin, cyclophosphamide, dactinomycin, methotrexate, cisplatin) plays a more critical role in osteosarcoma treatment (surface under the cumulative ranking (SUCRA) probability 76.9%), with a better effect on prolonging the PFS of patients when combined with ifosfamide (94.1%) or vincristine (81.9%). For the analysis of OS, we separated the regimens to two groups, reflecting the disconnection. The T12 protocol plus vincristine (94.7%) or the removal of cisplatinum (89.4%) is most likely the best regimen. We concluded that multi-drug regimens have a better effect on prolonging the PFS and OS of osteosarcoma patients, and the T12 protocol has a better effect on prolonging the PFS of osteosarcoma patients, particularly in combination with ifosfamide or vincristine

  19. Medical Management of Ectopic Pregnancy: A Comparison of Regimens

    Science.gov (United States)

    Bachman, Emelia Argyropoulos; Barnhart, Kurt

    2012-01-01

    Medical management has become increasingly popular in the treatment of ectopic pregnancy. Given its convenience, for many it is used as a first line treatment, but this is not always the optimal choice for the patient. It is important to understand the options for medical treatment and when it is appropriate to treat a particular patient with medical management, or when one should opt for surgical management. This review outlines the different regimens for methotrexate administration and the associated risks and benefits to medical management. PMID:22510626

  20. Galeazzi fractures: our modified classification and treatment regimen.

    Science.gov (United States)

    Fayaz, H C; Jupiter, J B

    2014-02-01

    While diaphyseal fractures of the forearm are a common orthopedic injury, Galeazzi fractures are difficult to treat. The current knowledge on pathobiomechanics and modified therapeutic decisions implicate the need to devise an updated classification and treatment regimen of Galeazzi fractures. We challenge the concept that isolated fractures of the radius should be considered as a Galeazzi fractures as long as stability of the distal radioulnar joint is not proven. Contrary to others we demonstrate that the fracture location alone is not sufficient to determine the stability of the distal radioulnar joint. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Microvascular blood flow dynamics associated with photodynamic therapy, pulsed dye laser irradiation and combined regimens.

    Science.gov (United States)

    Smith, Tia K; Choi, Bernard; Ramirez-San-Juan, Julio C; Nelson, J Stuart; Osann, Kathryn; Kelly, Kristen M

    2006-06-01

    Previous in vitro studies demonstrated the potential utility of benzoporphyrin derivative monoacid ring A (BPD) photodynamic therapy (PDT) for vascular destruction. Moreover, the effects of PDT were enhanced when this intervention was followed immediately by pulsed dye laser (PDL) irradiation (PDT/PDL). We further evaluate vascular effects of PDT alone, PDL alone and PDT/PDL in an in vivo rodent dorsal skinfold model. A dorsal skinfold window chamber was installed surgically on female Sprague-Dawley rats. One milligram per kilogram of BPD solution was administered intravenously via a jugular venous catheter. Evaluated interventions were: control (no BPD, no light), PDT alone (576 nm, 16 minutes exposure time, 15 minutes post-BPD injection, 10 mm spot), PDL alone at 7 J/cm2 (585 nm, 1.5 ms pulse duration, 7 mm spot), PDL alone at 10 J/cm2, PDT/PDL (PDL at 7 J/cm2), and PDT/PDL (PDL at 10 J/cm2). To assess changes in microvascular blood flow, laser speckle imaging was performed before, immediately after, and 18 hours post-intervention. Epidermal irradiation was accomplished without blistering, scabbing or ulceration. A reduction in perfusion was achieved in all intervention groups. PDT/PDL at 7 J/cm2 resulted in the greatest reduction in vascular perfusion (56%). BPD PDT can achieve safe and selective vascular flow reduction. PDT/PDL can enhance diminution of microvascular blood flow. Our results suggest that PDT and PDT/PDL should be evaluated as alternative therapeutic options for treatment of hypervascular skin lesions including port wine stain birthmarks. Copyright 2006 Wiley-Liss, Inc.

  2. Sequential regimen of clofarabine, cytosine arabinoside and reduced-intensity conditioned transplantation for primary refractory acute myeloid leukemia

    Science.gov (United States)

    Mohty, Mohamad; Malard, Florent; Blaise, Didier; Milpied, Noel; Socié, Gérard; Huynh, Anne; Reman, Oumédaly; Yakoub-Agha, Ibrahim; Furst, Sabine; Guillaume, Thierry; Tabrizi, Resa; Vigouroux, Stéphane; Peterlin, Pierre; El-Cheikh, Jean; Moreau, Philippe; Labopin, Myriam; Chevallier, Patrice

    2017-01-01

    The prognosis of patients with acute myeloid leukemia in whom primary treatment fails remains very poor. In order to improve such patients’ outcome, we conducted a phase 2, prospective, multicenter trial to test the feasibility of a new sequential regimen, combining a short course of intensive chemotherapy and a reduced intensity-conditioning regimen, before allogeneic stem-cell transplantation. Twenty-four patients (median age, 47 years) with acute myeloid leukemia in primary treatment failure were included. Cytogenetic risk was poor in 15 patients (62%) and intermediate in nine (38%). The sequential regimen consisted of clofarabine (30 mg/m2/day) and cytosine arabinoside (1 g/m2/day) for 5 days, followed, after a 3-day rest, by reduced-intensity conditioning and allogeneic stem-cell transplantation combining cyclophosphamide (60 mg/kg), intravenous busulfan (3.2 mg/kg/day) for 2 days and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Patients in complete remission at day +120 received prophylactic donor lymphocyte infusion. Eighteen patients (75%) achieved complete remission. With a median follow-up of 24.6 months, the Kaplan-Meier estimate of overall survival was 54% (95% CI: 33–71) at 1 year and 38% (95% CI: 18–46) at 2 years. The Kaplan-Meier estimate of leukemia-free survival was 46% (95% CI: 26–64) at 1 year and 29% (95% CI: 13–48) at 2 years. The cumulative incidence of non-relapse mortality was 8% (95% CI: 1–24) at 1 year and 12% (95% CI: 3–19) at 2 years. Results from this phase 2 prospective multicenter trial endorsed the safety and efficacy of a clofarabine-based sequential reduced-toxicity conditioning regimen, which warrants further investigation. This study was registered at www.clinicaltrials.gov, identifier number: NCT01188174. PMID:27561720

  3. A fixed-dose 24-hour regimen of artesunate plus sulfamethoxypyrazine-pyrimethamine for the treatment of uncomplicated Plasmodium falciparum malaria in eastern Sudan

    DEFF Research Database (Denmark)

    Adam, Ishag; Magzoub, Mamoun; Osman, Maha E

    2006-01-01

    -sulfamethoxypyrazine-pyrimethamine (AS+SMP f) administered at time intervals of 12 hours for a 24-hour therapy was compared with the efficacy of the same drug given as a loose combination (AS+SMP l) with a dose interval of 24 hours for 3 days for the treatment of uncomplicated Plasmodium falciparum malaria in eastern Sudan. RESULTS...... of the patients. CONCLUSION: both regimens of AS+SMP were effective and safe for the treatment of uncomplicated P. falciparum malaria in eastern Sudan. Due to its simplicity, the fixed dose one-day treatment regimen may improve compliance and therefore may be the preferred choice....

  4. Changes in insulin therapy regimens over 10 yr in children and adolescents with type 1 diabetes attending diabetes camps.

    Science.gov (United States)

    Redon, Isabelle; Beltrand, Jacques; Martin, Delphine; Taupin, Pierre; Choleau, Carine; Morandini, Mélina; Cahané, Michel; Robert, Jean-Jacques

    2014-08-01

    To describe the changes in insulin therapy regimens of children and adolescents with type 1 diabetes over 10 yr and their correlation with hemoglobin A1c (HbA1c). The study included 7206 children and adolescents (age 12.8 ± 2.7 yr, more than 1 yr of diabetes duration) admitted in summer camps between 1998 and 2007 (707-896/yr). Based on injection times (breakfast, lunch, afternoon, dinner, bedtime) and insulin types (short, long and premixed; human or analog), 786 different therapeutic combinations were classified in six main types of regimens. The distribution of the different regimens and their correlation with HbA1c were evaluated as a function of year and age. Over 10 yr, basal bolus increased from 13 to 52% and the pump from insulins from 33 to 7%, and diverse regimens from 9 to 1%. HbA1c was significantly higher with premixed insulin only, but there were no differences between the other regimens throughout the follow-up. Mean yearly HbA1c (8.21-8.45%) did not show any significant decrease, but the percentage of patients with HbA1c > 9 and 10% decreased significantly, in those treated with two to three injections and the pump, not with basal bolus or premixed only regimens. A major trend in intensifying insulin treatment in children and adolescents with type 1 diabetes was accompanied by modest improvements in HbA1c. No insulin regimen has shown any better results, except over premixed insulins. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Pig-to-baboon heterotopic heart transplantation--exploratory preliminary experience with pigs transgenic for human thrombomodulin and comparison of three costimulation blockade-based regimens.

    Science.gov (United States)

    Iwase, Hayato; Ekser, Burcin; Satyananda, Vikas; Bhama, Jay; Hara, Hidetaka; Ezzelarab, Mohamed; Klein, Edwin; Wagner, Robert; Long, Cassandra; Thacker, Jnanesh; Li, Jiang; Zhou, Hao; Jiang, Maolin; Nagaraju, Santosh; Zhou, Huidong; Veroux, Massimiliano; Bajona, Pietro; Wijkstrom, Martin; Wang, Yi; Phelps, Carol; Klymiuk, Nikolai; Wolf, Eckhard; Ayares, David; Cooper, David K C

    2015-01-01

    Three costimulation blockade-based regimens have been explored after transplantation of hearts from pigs of varying genetic backgrounds to determine whether CTLA4-Ig (abatacept) or anti-CD40mAb+CTLA4-Ig (belatacept) can successfully replace anti-CD154mAb. All pigs were on an α1,3-galactosyltransferase gene-knockout/CD46 transgenic (GTKO.CD46) background. Hearts transplanted into Group A baboons (n=4) expressed additional CD55, and those into Group B (n=3) expressed human thrombomodulin (TBM). Immunosuppression included anti-thymocyte globulin with anti-CD154mAb (Regimen 1: n=2) or abatacept (Regimen 2: n=2) or anti-CD40mAb+belatacept (Regimen 3: n=2). Regimens 1 and 2 included induction anti-CD20mAb and continuous heparin. One further baboon in Group B (B16311) received a modified Regimen 1. Baboons were followed by clinical/laboratory monitoring of immune/coagulation parameters. At biopsy, graft failure, or euthanasia, the graft was examined by microscopy. Group A baboons survived 15 to 33 days, whereas Group B survived 52, 99, and 130 days, respectively. Thrombocytopenia and reduction in fibrinogen occurred within 21 days in Group A, suggesting thrombotic microangiopathy (TM), confirmed by histopathology. In Group B, with follow-up for >4 m, areas of myofiber degeneration and scarring were seen in two hearts at necropsy. A T-cell response was documented only in baboons receiving Regimen 2. The combination of anti-CD40mAb+belatacept proved effective in preventing a T-cell response. The expression of TBM prevented thrombocytopenia and may possibly delay the development of TM and/or consumptive coagulopathy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Relapse of Helicobacter pylori infection after different treatment regimens. A 3-month follow-up study.

    Science.gov (United States)

    Nanivadekar, S A; Sawant, P D; Patel, H D; Shroff, C P; Popat, U R; Bhatt, P P

    1990-09-01

    Helicobacter pylori infection of gastric antrum is associated with a majority of cases of peptic ulcer (70-100%). Studies have shown that when this organism is eradicated, the recurrence of ulcer falls to less than one-third of those in whom the infection persists or relapses. Monotherapy with bismuth salts, tinidazone or amoxycillin has been shown to result in early relapse and recurrence of ulcers. However, dual or triple therapy regimens are more effective. We conducted a randomised controlled study using tripotassium dicitrato bismuthate (TDB) (10 patients); amoxycillin (combined with ranitidine for ulcer healing) (9 patients) and dual therapy with both amoxycillin and TDB (10 patients). Our study showed that relapse rates at the end of 3 months was significantly less if dual therapy with TDB and amoxycillin is used as compared to TDB alone (p less than 0.05).

  7. Identification of combinatorial drug regimens for treatment of Huntington's disease using Drosophila

    Science.gov (United States)

    Agrawal, Namita; Pallos, Judit; Slepko, Natalia; Apostol, Barbara L.; Bodai, Laszlo; Chang, Ling-Wen; Chiang, Ann-Shyn; Michels Thompson, Leslie; Marsh, J. Lawrence

    2005-03-01

    We explore the hypothesis that pathology of Huntington's disease involves multiple cellular mechanisms whose contributions to disease are incrementally additive or synergistic. We provide evidence that the photoreceptor neuron degeneration seen in flies expressing mutant human huntingtin correlates with widespread degenerative events in the Drosophila CNS. We use a Drosophila Huntington's disease model to establish dose regimens and protocols to assess the effectiveness of drug combinations used at low threshold concentrations. These proof of principle studies identify at least two potential combinatorial treatment options and illustrate a rapid and cost-effective paradigm for testing and optimizing combinatorial drug therapies while reducing side effects for patients with neurodegenerative disease. The potential for using prescreening in Drosophila to inform combinatorial therapies that are most likely to be effective for testing in mammals is discussed. combinatorial treatments | neurodegeneration

  8. Patterns of peripheral neuropathy in ART-naïve patients initiating modern ART regimen.

    Science.gov (United States)

    Lee, Anthony J; Bosch, Ronald J; Evans, Scott R; Wu, Kunling; Harrison, Taylor; Grant, Philip; Clifford, David B

    2015-04-01

    The purpose of this study was to evaluate associations of pre-ART CD4 with peripheral neuropathy (PN) and estimate the prevalence of PN in HIV-positive patients starting modern combination antiretroviral therapy (cART) regimens. ART-naïve subjects initiating cART were followed longitudinally and screened for signs/symptoms of PN. Lower pre-ART CD4 count was associated with post-ART PN. After 7 years (n = 117), the prevalence (95% CI) of PN and SPN were 31% (23, 40%) and 5% (2, 11%) with pre-ART CD4 count >250 copies/μL. PN continues to be identified in HIV-infected individuals on modern cART by targeted assessment but is generally without symptoms.

  9. Atypical Amniotic Fluid Embolism Managed with a Novel Therapeutic Regimen

    Directory of Open Access Journals (Sweden)

    Shadi Rezai

    2017-01-01

    Full Text Available Amniotic fluid embolism (AFE is the second leading cause of maternal mortality in the USA with an incidence of 1 : 15,200 births. The case fatality rate and perinatal mortality associated with AFE are 13–30% and 9–44%, respectively. This rare but devastating complication can be difficult to diagnose as many of the early signs and symptoms are nonspecific. Compounding this diagnostic challenge is a lack of effective treatment regimens which to date are mostly supportive. We present the case of a 26-year-old woman who suffered from suspected AFE and was successfully treated with the novel regimen of Atropine, Ondansetron, and Ketorolac (A-OK. The authors acknowledge that this case does not meet the new criteria proposed, by Clark in 2016, but feel that it is important to share this case report, due to dramatic patient response to the provided supportive therapy presented in this case report. We hope this case report will prompt further research into this novel approach to treating AFE with Atropine, Ondansetron, and Ketorolac.

  10. Late effects of various dose-fractionation regimens

    International Nuclear Information System (INIS)

    Turesson, I.; Notter, G.

    1983-01-01

    These clinical investigations of various dose-fractionation regimens on human skin show that: The late reactions cannot be predicted from the early reactions; The dose-response curves for late reactions are much steeper than for early reactions; Equivalent doses for various fractionation schedules concerning late effects can be calculated by means of a corrected CRE (NSD) formula; the correction must be considered preliminary because further follow-up is needed. A clinical fractionation study of this type requires: Extremely careful dosimetry; Study of the same anatomical region; Very long follow-up; Studies at different effect levels; Skin reaction is the only end point we have studied systematically for different fractionation regimens. Experience with the CRE formula as a model for calculating isoeffect doses for different fractionation schedules in routine clinical use can be summarized as follows: The CRE formula has been used prospectively since 1972 in all patients; CRE-equivalent weekly doses to 5 x 2.0 Gy per week has been used. (Although the fractionation schedule is changed, the overall treatment time is still the same); The CRE range was 18 to 21 for curative radiotherapy on carcinomas; No irradiation was applied during pronounced acute reactions. No unexpected complications have been observed under these conditions

  11. Postcesarean Thromboprophylaxis with Two Different Regimens of Bemiparin

    Directory of Open Access Journals (Sweden)

    Milagros Cruz

    2011-01-01

    Full Text Available Objectives. To compare the effectiveness of postcesarean thromboprophylaxis with two different regimens of bemiparin. Material and Methods. The study included 646 women with cesarean delivery in our hospital within a 1-year period, randomly assigned to one of two groups for prophylaxis with 3500 IU bemiparin once daily for 5 days or 3500 IU bemiparin once daily for 10 days. Results. There was one case of pulmonary embolism (first day following cesarean. An additional risk factor was present in 98.52% of the women, most frequently emergency cesarean, anemia, or obesity. The only risk factors for thromboembolic disease significantly related to pulmonary thromboembolism were placental abruption and prematurity. There were no differences in thromboembolic events among the two thromboprophylaxis regimens. Conclusions. Cesarean-related thromboembolic events were reduced in our study population due to the thromboprophylactic measures taken. Thromboprophylaxis with 3500 IU bemiparin once daily for 5 days following cesarean was sufficient to avoid thromboembolic events.

  12. Sofosbuvir/velpatasvir regimen promises an effective pan-genotypic hepatitis C virus cure

    Directory of Open Access Journals (Sweden)

    Mir F

    2017-02-01

    Full Text Available Fazia Mir, Alp S Kahveci, Jamal A Ibdah, Veysel Tahan Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO, USA Abstract: Hepatitis C virus (HCV is a global pandemic, with nearly 200 million infected patients worldwide. HCV is the most common blood-borne infection in the US with numerous health implications including liver fibrosis, cirrhosis, and hepatocellular cancer. Traditional genotype-based HCV therapies with interferon resulted in moderate success in the sustained elimination of viral genome. Recent clinical trials of the once-daily combination tablet of sofosbuvir, a nonstructural (NS 5B polymerase inhibitor, and velpatasvir, an NS5A inhibitor, demonstrate sustained virologic response rates of about 95%, regardless of prior treatment experience or presence of cirrhosis across all HCV genotypes. Patients reported improvements in general health, fatigue, and emotional and mental well-being after completing combination therapy. The combination treatment is effective, but does need to be administered with caution in patients receiving certain medications or with certain diseases. Herein, we review the safety and efficacy of sofosbuvir/velpatasvir combination regimen for all HCV genotypes. Keywords: sofosbuvir, velpatasvir, hepatitis C, treatment, pan-genotypic, genotype

  13. Effectiveness of three oral hygiene regimens on oral malodor reduction: a randomized clinical trial.

    Science.gov (United States)

    Aung, Ei Ei; Ueno, Masayuki; Zaitsu, Takashi; Furukawa, Sayaka; Kawaguchi, Yoko

    2015-01-27

    Breath odor is a nuisance problem for many people around the world. Bad breath affects social interactions of people in daily life by causing personal discomfort and emotional stress. There are chemical and mechanical methods for controlling oral malodor. Many studies of various mouth rinse applications and tongue cleaning procedures have been conducted. However, few studies have compared the effect of simultaneous chemical and mechanical procedures on the reduction of volatile sulfur compounds (VSCs) in subjects with oral malodor. The purpose of this study was to assess the effects of different oral hygiene procedures on reduction of VSCs in subjects with oral malodor. Thirty male volunteers who matched with study criteria were divided randomly into two groups. Both groups performed tooth brushing, mouth washing with chlorine dioxide, tongue cleaning and combination of those in different sequence for five weeks. Total VSCs of subjects were measured with a Breathtron®, and oral health status was also examined. Quantitative analyses were performed using the Statistical Package for Social Science (SPSS 16.0). There were no significant differences in oral health status between the two groups at the baseline. No significant decrease in oral malodor was detected after one week of tooth brushing. Significant reductions in VSCs were shown by adding mouthwash or tongue cleaning to tooth brushing from the second week to fourth week (P oral hygiene regimens. Tooth brushing alone does not significantly reduce oral malodor. Mouth washing and tongue cleaning significantly reduce oral malodor, but combining tooth brushing, mouth washing and tongue cleaning regimens is most effective for oral malodor reduction. The results of this study could contribute to the formulation of appropriate preventive strategies against oral malodor not only for the general public but also for dental professionals serving as oral malodor-related service providers. Registration number - Clinical

  14. [Successful treatment with high-dose methotrexate/cytarabine regimen in a patient in SMILE regimen-resistant extranodal natural killer/T-cell lymphoma].

    Science.gov (United States)

    Saburi, Masuho; Itani, Kazuhito; Nagamatsu, Kentarou; Miyazaki, Yasuhiko; Otsuka, Eiichi; Urabe, Shogo; Saburi, Yoshio

    2014-01-01

    A 28-year-old man complained of pain in the oral mucosa and pharynx in March 2011, and then developed fever and generalized swelling of the cheek. In March 2012, a gum biopsy led to a diagnosis of extranodal natural killer/T-cell lymphoma (ENKL). (18)F-FDG-PET revealed significant uptake in the mouth, tonsils, jawbone, shoulder blade, humerus, ilium, femur, and spleen. After two courses of the SMILE (dexamethasone, methotrexate (MTX), ifosfamide, L-asparaginase, etoposide) regimen, the response was stable disease. However, a high-dose MTX/cytarabine (MA) regimen was effective. After three courses of the MA regimen, a partial response was achieved. Then, allogeneic bone marrow transplantation from an unrelated donor was performed. At 10 months after transplantation, there was no sign of recurrence. Although the optimal treatment for ENKL refractory to the SMILE regimen has yet to be established, our case suggests the MA regimen to be a potentially effective treatment option.

  15. Use of an integrated modelling and simulation approach to develop a simplified peginterferon alfa-2a dosing regimen for children with hepatitis C.

    Science.gov (United States)

    Brennan, Barbara J; Lemenuel-Diot, Annabelle; Snoeck, Eric; McKenna, Michael; Solsky, Jonathan; Wat, Cynthia; Mallalieu, Navita L

    2016-04-01

    The aim of the study was to simplify the dosing regimen of peginterferon alfa-2a in paediatric patients with chronic hepatitis C. A population pharmacokinetic (PK) model was developed using PK data from 14 children aged 2-8 years and 402 adults. Simulations were produced to identify a simplified dosing regimen that would provide exposures similar to those observed in the paediatric clinical trials and in the range known to be safe/efficacious in adults. Model predictions were evaluated against observed adult and paediatric data to reinforce confidence of the proposed dosing regimen. The final model was a two compartment model with a zero order resorption process. Covariates included a linear influence of body surface area (BSA) on apparent oral clearance (CL/F) and a linear influence of body weight on apparent volume of distribution of the central compartment (V1 /F). A simplified dosing regimen was developed which is expected to provide exposures in children aged ≥5 years similar to the dosing formula used in the paediatric clinical trial and within the range that is safe/efficacious in adults. This simplified regimen is approved in the EU and in other countries for the treatment of chronic hepatitis C in treatment-naive children/adolescents aged ≥5 years in combination with ribavirin. Pre-existing adult PK data were combined with relatively limited paediatric PK data to develop a PK model able to predict exposure in both populations adequately. This provided increased confidence in characterizing PK in children and helped in the development of a simplified dosing regimen of peginterferon alfa-2a in paediatric patients. © 2015 The British Pharmacological Society.

  16. Therapeutic strategy for pandrug-resistant Klebsiella pneumoniae severe infections: short-course treatment with colistin increases the in vivo and in vitro activity of double carbapenem regimen

    Directory of Open Access Journals (Sweden)

    Alessandra Oliva

    2015-04-01

    Full Text Available Infections due to carbapenemase-producing Klebsiella pneumoniae represent an emerging threat due to the high mortality rate and lack of valid antimicrobial combinations, especially when the strain is colistin-resistant. We report a case of bloodstream infection due to pandrug-resistant K. pneumoniae treated successfully with an innovative regimen comprising a combination of colistin plus double carbapenem, along with an in vitro analysis showing the synergistic and bactericidal effect.

  17. The clinical efficacy of a clarithromycin-based regimen for Mycobacterium avium complex disease: A nationwide post-marketing study.

    Science.gov (United States)

    Kadota, Jun-Ichi; Kurashima, Atsuyuki; Suzuki, Katsuhiro

    2017-05-01

    The revised 2007 American Thoracic Society/Infectious Diseases Society of America statement recommend clarithromycin-based combination therapy for treatment of Mycobacterium avium complex lung disease and stipulates approximately 1 year of continuous treatment after bacilli negative conversion. However, supporting data are insufficient. Our objective was to obtain data on the clinical outcome of clarithromycin-based daily regimens by conducting a nationwide retrospective post-marketing study of M. avium complex lung disease. In accordance with the Japanese guidelines, patients were enrolled in this survey according to their chest radiographic findings and microbiologic test results. They were treated with a multidrug regimen including clarithromycin, rifampicin, and ethambutol (clarithromycin-based regimen) until bacilli negative conversion, and the treatment was continued for approximately 1 year after the initial conversion. Data were collected before administration, at the time of bacilli negative conversion, at the end of treatment, and at 6 months after the end of treatment. Of the 466 subjects enrolled in the study, 271 patients who received clarithromycin at 800 mg/day underwent evaluation for M. avium complex disease. The final bacilli negative conversion rate in those patients was 94.7%. The bacteriological relapse rate was 5.0% (5/100 patients). Bacteriological relapse was noted in patients treated for less than 15 months after conversion. No life-threatening or serious adverse drug reactions were observed. This study demonstrated that a clarithromycin-based daily regimen can yield a high bacteriological conversion rate in M. avium complex disease. After conversion, treatment for less than 15 months might be insufficient to prevent bacteriological relapse. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  18. Paclitaxel and Carboplatin (TC) Regimen for Ovarian Cancer.

    Science.gov (United States)

    Akin, Julie M; Waddell, J Aubrey; Solimando, Dominic A

    2014-05-01

    The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net.

  19. nab-Paclitaxel Plus Gemcitabine Regimen for Pancreatic Cancer.

    Science.gov (United States)

    Porter, Courtney E; Waddell, J Aubrey; Solimando, Dominic A

    2014-01-01

    The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc, 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net.

  20. Antirelapse Efficacy of Various Primaquine Regimens for Plasmodium vivax

    Directory of Open Access Journals (Sweden)

    D. D. Rajgor

    2014-01-01

    respectively P=0.004. The relapse rate was 6.89%, 1.55%, 4%, and 3.85% as per the month of recurrence; 8.2%, 2%, 4.58%, and 3.68% P=0.007 as per PCR-RFLP; and 2.73%, 1.47%, 1.55%, and 1.53% as per PCR sequencing for groups A, B, C, and D, respectively. The concordance between methods was low, 45%. Conclusion. The higher recurrence rate in no PQ as compared to PQ groups documents PQ antirelapse activity. Regimens tested were safe. However, probable resistance to PQ warrants continuous monitoring and low concordance and limitations in the methods warrant caution in interpreting.

  1. Medication regimen complexity in ambulatory older adults with heart failure

    Directory of Open Access Journals (Sweden)

    Cobretti MR

    2017-04-01

    Full Text Available Michael R Cobretti,1 Robert L Page II,2 Sunny A Linnebur,2 Kimberly M Deininger,1 Amrut V Ambardekar,3 JoAnn Lindenfeld,4 Christina L Aquilante1 1Department of Pharmaceutical Sciences, 2Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, 3Division of Cardiology, School of Medicine, University of Colorado, Aurora, CO, 4Advanced Heart Failure and Cardiac Transplant Program, Vanderbilt Heart and Vascular Institute, Nashville, TN, USA Purpose: Heart failure prevalence is increasing in older adults, and polypharmacy is a major problem in this population. We compared medication regimen complexity using the validated patient-level Medication Regimen Complexity Index (pMRCI tool in “young-old” (60–74 years versus “old-old” (75–89 years patients with heart failure. We also compared pMRCI between patients with ischemic cardiomyopathy (ISCM versus nonischemic cardiomyopathy (NISCM.Patients and methods: Medication lists were retrospectively abstracted from the electronic medical records of ambulatory patients aged 60–89 years with heart failure. Medications were categorized into three types – heart failure prescription medications, other prescription medications, and over-the-counter (OTC medications – and scored using the pMRCI tool.Results: The study evaluated 145 patients (n=80 young-old, n=65 old-old, n=85 ISCM, n=60 NISCM, mean age 73±7 years, 64% men, 81% Caucasian. Mean total pMRCI scores (32.1±14.4, range 3–84 and total medication counts (13.3±4.8, range 2–30 were high for the entire cohort, of which 72% of patients were taking eleven or more total medications. Total and subtype pMRCI scores and medication counts did not differ significantly between the young-old and old-old groups, with the exception of OTC medication pMRCI score (6.2±4 young-old versus 7.8±5.8 old-old, P=0.04. With regard to heart failure etiology, total pMRCI scores and medication

  2. Immunogenicity, safety and antibody persistence of a purified vero cell cultured rabies vaccine (Speeda) administered by the Zagreb regimen or Essen regimen in post-exposure subjects.

    Science.gov (United States)

    Shi, Nianmin; Zhang, Yibin; Zheng, Huizhen; Zhu, Zhenggang; Wang, Dingming; Li, Sihai; Li, Yuhua; Yang, Liqing; Zhang, Junnan; Bai, Yunhua; Lu, Qiang; Zhang, Zheng; Luo, Fengji; Yu, Chun; Li, Li

    2017-06-03

    To compare the safety, immunogenicity and long-term effect of a purified vero cell cultured rabies vaccine in post-exposure subjects following 2 intramuscular regimens, Zagreb or Essen regimen. Serum samples were collected before vaccination and on days 7, 14, 42, 180 and 365 post vaccination. Solicited adverse events were recorded for 7 d following each vaccine dose, and unsolicited adverse events throughout the entire study period. This study was registered with ClinicalTrials.gov (NCT01821911 and NCT01827917). No serious adverse events were reported. Although Zagreb regimen had a higher incidence of adverse reactions than Essen regimen at the first and second injection, the incidence was similar at the third and fourth injection between these 2 groups as well. At day 42, 100% subjects developed adequate rabies virus neutralizing antibody concentrations (≥ 0.5IU/ml) for both regimens. At days 180 and 365, the antibody level decreased dramatically, however, the percentage of subjects with adequate antibody concentrations still remained high (above 75% and 50% respectively). None of confirmed rabies virus exposured subjects had rabies one year later, and percentage of subjects with adequate antibody concentrations reached 100% at days 14 and 42. Rabies post-exposure prophylaxis vaccination with PVRV following a Zagreb regimen had a similar safety, immunogenicity and long-term effect to the Essen regimen in China.

  3. Bendamustine mitoxantrone and rituximab (BMR): a new effective regimen for refractory or relapsed indolent lymphomas.

    Science.gov (United States)

    Weide, Rudolf; Heymanns, Jochen; Gores, Annette; Köppler, Hubert

    2002-02-01

    Bendamustine (B) and mitoxantrone (M) have been shown to be potent cytotoxic drugs for the treatment of relapsed or refractory indolent lymphomas. The anti-CD20 monoclonal antibody rituximab (R) has produced an overall response rate (ORR) of 50% as a single agent in relapsed or refractory indolent lymphomas. We posed the question whether a combination of the above agents (BMR) could improve these results. This study was an open label, single center pilot study for patients with relapsed or refractory, CD20-positive (indolent) lymphoma or chronic lymphocytic leukaemia. The therapy consisted of bendamustine (80 mg/m2, day 1-3), mitoxantrone (10 mg/m2, day 1), rituximab (375 mg/m2, week 2-5). BM was repeated on day 36 or when the haematological parameters had recovered. The maximum therapy consisted of one BMR-cycle, followed by five BM courses. Treatment was stopped when the disease responded with PR/CR. During March 1999 and December 2000, 20 patients received the BMR-regimen (four secondary high grade lymphoma, 12 indolent lymphoma, four B-CLL). The median age of the patients was 67 years (range 36-82) and their performance status ranged from 0 to 3. Median number of previous treatment regimens was two (1-6). Of the lymphoma patients, 14 had stage IV disease, 1 stage III and 1 stage II. B-CLL patients were all Rai stage IV (Binet C). Overall response rate was 95% (19/20) with seven patients achieving a CR (35%) and 12 patients achieving a PR (60%). Median time to progression is 7 months (1-21) with a median observation time of 7 months (1-21). Response is still durable in 15/20 patients (75%) (1+ to 21+ months after therapy). Symptomatic, reversible grade three or four haematotoxicity occurred in 4/20 patients (20%). Non-symptomatic grade three or four haematotoxicity was seen in 9/20 patients (45%). No major non-haematological toxicity was observed. In conclusion, BMR is a well tolerated, very effective outpatient regimen of treatment for relapsed and refractory

  4. Comparative efficacy of two regimens in syndromic management of lower genital infections.

    Science.gov (United States)

    Sharma, J B; Mittal, Suneeta; Raina, Usha; Chanana, Charu

    2006-01-01

    The aim of this study was to compare the efficacy and safety of two combination regimens in the syndromic management of lower genital infection. Seventy-two non-pregnant women presenting with symptoms of lower genital infection diagnosed as vaginitis on clinical examination and lacking obvious upper genital infection were enrolled to one of the two treatment regimens as a syndromic treatment. No investigations were performed to cut the cost and to avoid the loss of patients on follow-up. Thirty-seven women (group I) were prescribed a course of clotrimazole (Imidil, Lyka) 100 mg vaginal pessaries for 6 days. Along with their partners they were prescribed 2 gm secnidazole (Secnil forte) and 150 mg fluconazole (Syscan) as a single therapy. Thirty-five women (group II) were prescribed vaginal clotrimazole as mentioned above. A combination kit containing 150 mg fluconazole, 2 gm secnidazole and 1 gm azithromycin (FAS-3 kit, Lyka) was also prescribed to both partners with the advice to take azithromycin on empty stomach, and the other three tablets after food. All women in both groups were seen after 1 week for relief of symptoms and after 1 month for any recurrence. Mean parity was 2.7 and 3.0, respectively. The total symptomatic relief was observed in 67.6 and 94.3% cases, partial relief in 27 and 5.7% cases and no relief was observed in 5.4% and nil cases, respectively, in the two groups. Recurrence was seen in two and nil cases, respectively, in the two groups. Most women tolerated both the treatments well with no major side effect in any case. Treatment cost was higher in group II (Rupees 120) than in group I (Rupees 65). Both combination kits with local clotrimazole were reasonably effective and safe in the syndromic approach for lower genital infections. The combination kit with azithromycin, secnidazole and fluconazole was more effective with better symptomatic relief and less recurrence rate and may be routinely recommended in all cases of lower genital

  5. Pan-genotypic treatment regimens for hepatitis C virus: Advantages and disadvantages in high- and low-income regions.

    Science.gov (United States)

    Hézode, C

    2017-02-01

    During the last 5 years, the availability of direct-acting antiviral (DAA) agents has revolutionized the treatment of hepatitis C virus (HCV). Compared with interferon/ribavirin-the previous standard of care-DAA combination regimens offer improved sustained virological response (SVR) rates, shorter treatment durations of 8-24 weeks, convenient once-daily single-tablet formulations and more favourable tolerability profiles. HCV treatment is complex, and the choice of therapy must consider a complex range of factors, including baseline viral load, fibrosis stage, the HCV genotype and subgenotype, and the presence of resistance-associated substitutions at baseline. Globally, HCV genotype 1 predominates, and there are extensive data and various treatment options available for this genotype. Genotypes 2-6 are prevalent and may even predominate in different geographical regions, reflecting diverse factors including human migration patterns and unsafe use of injection drugs and blood products. Such factors are themselves influenced by socio-economic factors, and poor regions often have the greatest unmet need for effective HCV therapies. The latest pan-genotypic DAA combination regimens provide the potential to eradicate HCV around the globe, regardless of genotype, hence minimizing the need for virological testing services, which often are unavailable in poorer regions. Economics inevitably remain a barrier to access, and extensive cooperation will be required between clinical organisations and pharmaceutical manufacturers to agree appropriate pricing policies, especially in poorer economic regions. This review considers key data and treatment guidelines for DAA therapies, including pan-genotypic combination regimens, in the context of regional differences in HCV genotype and socio-economic factors. © 2016 John Wiley & Sons Ltd.

  6. Patients' Willingness to Take Multiple-Tablet Antiretroviral Therapy Regimens for Treatment of HIV.

    Science.gov (United States)

    Engelhard, Esther A N; Smit, Colette; Vervoort, Sigrid C J M; Smit, Peter J; Nieuwkerk, Pythia T; Kroon, Frank P; Reiss, Peter; Brinkman, Kees; Geerlings, Suzanne E

    2016-06-01

    The costs of combination antiretroviral therapy (cART) for HIV, consisting of separate, particularly generic, components (multiple-tablet regimens, MTR) are generally much lower than those of single-tablet regimens (STR) comprising the same active ingredients. To assess whether patients would be willing to take MTR, once-daily, instead of STR, with the goal of reducing general healthcare costs. In addition, we aimed to examine whether willingness was associated with particular patient characteristics. Data from the ATHENA cohort database in The Netherlands of adult HIV-1-infected patients in care and taking cART ≥6 months were used to select 1000 potential participants for an online patient survey on patient preferences and satisfaction. Participants were asked whether they would be willing to take three pills with the equivalent active ingredients simultaneously instead of STR to reduce costs. Multivariate logistic regression was used to examine associations between patient characteristics and willingness to take MTR instead of STR. Forty-seven percent ( n  = 152) of the 322 respondents answered 'yes' and 26 % ( n  = 83) answered 'maybe' when asked whether they would be willing to take three pills with the equivalent active ingredients simultaneously to reduce costs. Non-Dutch patients were significantly more likely to answer 'no' (OR: 2.49; 95 % CI: 1.17-5.30) or 'maybe' (OR: 2.63; 95 % CI: 1.24-5.60). Answering 'no' was less common among patients who had been taking cART ≥15 years (OR: 0.23; 95 % CI: 0.09-0.58). Commonly reported concerns included the dosing frequency, efficacy and tolerability of MTR. HIV-infected patients do not necessarily oppose the decision to prescribe MTR instead of STR to reduce healthcare costs. However, the potential trade-off in terms of convenience should be carefully weighed against the projected savings.

  7. Neoadjuvant Therapy of DOF Regimen Plus Bevacizumab Can Increase Surgical Resection Ratein Locally Advanced Gastric Cancer

    Science.gov (United States)

    Ma, Junxun; Yao, Sheng; Li, Xiao-Song; Kang, Huan-Rong; Yao, Fang-Fang; Du, Nan

    2015-01-01

    Abstract Locally advanced gastric cancer (LAGC) is best treated with surgical resection. Bevacizumab in combination with chemotherapy has shown promising results in treating advanced gastric cancer. This study aimed to investigate the efficacy of neoadjuvant chemotherapy using the docetaxel/oxaliplatin/5-FU (DOF) regimen and bevacizumab in LAGC patients. Eighty LAGC patients were randomized to receive DOF alone (n = 40) or DOF plus bevacizumab (n = 40) as neoadjuvant therapy before surgery. The lesions were evaluated at baseline and during treatment. Circulating tumor cells (CTCs) were counted using the FISH test. Patients were followed up for 3 years to analyze the disease-free survival (DFS) and overall survival (OS). The total response rate was significantly higher in the DOF plus bevacizumab group than the DOF group (65% vs 42.5%, P = 0.0436). The addition of bevacizumab significantly increased the surgical resection rate and the R0 resection rate (P DOF plus bevacizumab group showed significantly greater reduction in CTC counts after neoadjuvant therapy in comparison with the DOF group (P = 0.0335). Although the DOF plus bevacizumab group had significantly improved DFS than the DOF group (15.2 months vs 12.3 months, P = 0.013), the 2 groups did not differ significantly in OS (17.6 ± 1.8 months vs 16.4 ± 1.9 months, P = 0.776. Cox proportional model analysis showed that number of metastatic lymph nodes, CTC reduction, R0 resection, and neoadjuvant therapy are independent prognostic factors for patients with LAGC. Neoadjuvant of DOF regimen plus bevacizumab can improve the R0 resection rate and DFS in LAGC. These beneficial effects might be associated with the reduction in CTC counts. PMID:26496252

  8. Elicitation of Both Anti HIV-1 Env Humoral and Cellular Immunities by Replicating Vaccinia Prime Sendai Virus Boost Regimen and Boosting by CD40Lm

    Science.gov (United States)

    Zhang, Xianfeng; Sobue, Tomoyoshi; Isshiki, Mao; Makino, Shun-ichi; Inoue, Makoto; Kato, Kazunori; Shioda, Tatsuo; Ohashi, Takashi; Sato, Hirotaka; Komano, Jun; Hanabusa, Hideji; Shida, Hisatoshi

    2012-01-01

    For protection from HIV-1 infection, a vaccine should elicit both humoral and cell-mediated immune responses. A novel vaccine regimen and adjuvant that induce high levels of HIV-1 Env-specific T cell and antibody (Ab) responses was developed in this study. The prime-boost regimen that used combinations of replication-competent vaccinia LC16m8Δ (m8Δ) and Sendai virus (SeV) vectors expressing HIV-1 Env efficiently produced both Env-specific CD8+ T cells and anti-Env antibodies, including neutralizing antibodies (nAbs). These results sharply contrast with vaccine regimens that prime with an Env expressing plasmid and boost with the m8Δ or SeV vector that mainly elicited cellular immunities. Moreover, co-priming with combinations of m8Δs expressing Env or a membrane-bound human CD40 ligand mutant (CD40Lm) enhanced Env-specific CD8+ T cell production, but not anti-Env antibody production. In contrast, priming with an m8Δ that coexpresses CD40Lm and Env elicited more anti-Env Abs with higher avidity, but did not promote T cell responses. These results suggest that the m8Δ prime/SeV boost regimen in conjunction with CD40Lm expression could be used as an immunization platform for driving both potent cellular and humoral immunities against pathogens such as HIV-1. PMID:23236521

  9. Systemic combination treatment for psoriasis: a review

    DEFF Research Database (Denmark)

    Jensen, Peter; Skov, Lone; Zachariae, Claus

    2010-01-01

    Psoriasis is a chronic inflammatory skin disease, which affects approximately 2.6% of the population in Northern Europe and Scandinavia. In order to achieve disease control, combinations of systemic treatments are sometimes needed for variable time periods. However, no evidence-based guidelines...... exist for the use of systemic combination therapy. Therefore, our aim was to review the current literature on systemic anti-psoriatic combination regimens. We searched PubMed and identified 98 papers describing 116 studies (23 randomized) reporting on the effect of various systemic combination...... treatments. The most thoroughly investigated combination was retinoid and phototherapy. Further controlled research is needed to define the safest and most effective combination regimens....

  10. Salvage Regimens Containing Darunavir, Etravirine, Raltegravir, or Enfuvirtide in Highly Treatment-Experienced Perinatally Infected Pregnant Women.

    Science.gov (United States)

    Shust, Gail F; Jao, Jennifer; Rodriguez-Caprio, Gabriela; Posada, Roberto; Chen, Katherine T; Averitt, Amelia; Sperling, Rhoda S

    2014-09-01

    Combination antiretroviral therapy in pregnant women with human immunodeficiency virus has dramatically decreased maternal-to-child transmission. Highly treatment-experienced pregnant patients have limited effective treatment options due to past toxicities and viral resistance. We present 8 pregnancies in 7 perinatally infected women successfully treated with salvage regimens containing darunavir, etravirine, raltegravir, or enfuvirtide. © The Author 2013. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. Development of a chemotherapy regimen interaction database for the mobile internet: detecting interactions with psychotropics through OncoRx-MI.

    Science.gov (United States)

    Yap, Kevin Yi-Lwern; Chui, Wai Keung; Chan, Alexandre

    2011-09-01

    Cancer patients are at high risks of drug-drug interactions (DDIs). Clinicians need to know the magnitude of DDIs so as to better manage their patients' drug therapies. We have previously created a novel interaction database for oncology prescriptions (OncoRx). In this project, we leverage on 3G networks to further develop this database into an iPhone-specific application for the mobile internet (OncoRx-MI). Data on anticancer drugs (ACDs), chemotherapy regimens (CRegs) and DDIs with psychotropics were compiled from various hardcopy and online resources, and published articles from PubMed, Scopus and Science Direct. The database and iPhone web documents were designed using Adobe Dreamweaver CS4 and associated with a combination of open-source programming scripts. OncoRx-MI currently detects over 5000 DDIs (69.3% pharmacokinetic, 30.7% pharmacodynamic) between 256 single-agent and combination CRegs with 51 psychotropic drugs. OncoRx-MI fits the iPhone screen configuration, and displays information regarding the regimen, pharmacokinetics of the drugs and detected DDIs in tabular format for improved usability. OncoRx-MI is the first mobile DDI application of its kind which detects interactions for combination CRegs. Future versions will include DDIs with other drug categories. Usability studies on its impact in clinical practice will also be carried out.

  12. Etoposide-Actinomycin as Salvage Regimen for the Treatment of Nonmetastatic and Low-Risk Metastatic Gestational Trophoblastic Neoplasia: Experience at the Philippine General Hospital.

    Science.gov (United States)

    Nevado-Gammad, Mariel S; Soriano-Estrella, Agnes L

    2016-06-01

    Single-agent chemotherapy has been the standard of treatment for nonmetastatic and metastatic low-risk gestational trophoblastic neoplasia (GTN). However, it is estimated that approximately 12% to 32% of patients given single-agent therapy will require a change of chemotherapy regimen because of drug resistance and/or intolerable toxicity. The Section of Trophoblastic Diseases of the Philippine General Hospital started using the combination of etoposide-actinomycin (EA) as salvage chemotherapy in the early 2000s. This study was carried out to describe the local experience with this salvage chemotherapy. This is a retrospective descriptive study aimed to analyze the efficacy and safety of the EA regimen as salvage treatment for the management of nonmetastatic and low-risk metastatic GTN. Records of the Section of Trophoblastic Diseases of the Philippine General Hospital from January 1, 2002 to June 30, 2014 were reviewed to identify all patients who had a diagnosis of nonmetastatic and metastatic low-risk GTN. Primary remission rate and toxicity profile of all patients who received the EA regimen as salvage treatment were determined. During the study period, a total of 67 cycles of the EA regimen were administered to 15 patients as salvage chemotherapy. Patients received a median of 4 cycles of EA, attaining normal serum beta human chorionic gonadotropin after 2 to 3 cycles. Thirteen of the 15 patients achieved complete remission with the EA regimen, giving a remission rate of 87%. The major toxicity that the patients experienced was myelosuppression. Grade 1/2 anemia was addressed by blood transfusion. Grade 3 neutropenia/myelosuppression was addressed by the administration of granulocyte colony-stimulating factor. Alopecia was seen in all of the patients. One patient experienced dermatitis with accompanying myelosuppression. The EA regimen was efficacious and well tolerated for the treatment of refractory nonmetastatic and low- risk metastatic GTN.

  13. A comparison of 3 antibiotic regimens for prevention of postcesarean endometritis: an historical cohort study.

    Science.gov (United States)

    Ward, Erin; Duff, Patrick

    2016-06-01

    Prophylactic antibiotics are of proven value in decreasing the frequency of postcesarean endometritis. The beneficial effect of prophylaxis is enhanced when the antibiotics are administered before the surgical incision as opposed to after the clamping of the umbilical cord. However, the optimal antibiotic regimen for prophylaxis has not been established firmly. The purpose of this study was to compare 3 different antibiotic regimens for the prevention of postcesarean endometritis. This retrospective historical cohort study was conducted at the University of Florida, which is a tertiary care facility that serves a predominantly indigent patient population. In the period January 2003 to December 2007, our standard prophylactic antibiotic regimen for all women who had cesarean delivery was cefazolin (1 g) administered immediately after the baby's umbilical cord was clamped. In November 2008, we began to administer the combined regimen of cefazolin (1 g intravenously) plus azithromycin (500 mg intravenously); both were given 30-60 minutes before the skin incision. In the period of January-December 2014, we continued the dual agent regimen but based the dose of cefazolin on the patient's body mass index: 2 g intravenously if the body mass index was 30 kg/m(2). The surgical technique was consistent throughout all 3 time periods. Our primary endpoint was the frequency of endometritis in each time period. This diagnosis was based on fever ≥37.5°C, lower abdominal pain and tenderness, the exclusion of other localizing signs of infection, and the requirement for administration of therapeutic antibiotics. In the first year after beginning the new antibiotic regimen, we also monitored the frequency of neonatal sepsis evaluations and compared it with the frequency that was recorded during the year immediately preceding the change in antibiotic regimens. During the entire period 2003-2014, 29,633 women delivered at our institution; 6455 women (22%) had a cesarean delivery. In

  14. Aggressive regimens for multidrug-resistant tuberculosis decrease all-cause mortality.

    Directory of Open Access Journals (Sweden)

    Carole D Mitnick

    Full Text Available A better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen.This study assessed the impact of an aggressive regimen-one containing at least five likely effective drugs, including a fluoroquinolone and injectable-on treatment outcomes in a large MDR-TB patient cohort.This was a retrospective cohort study of patients treated in a national outpatient program in Peru between 1999 and 2002. We examined the association between receiving an aggressive regimen and the rate of death.In total, 669 patients were treated with individualized regimens for laboratory-confirmed MDR-TB. Isolates were resistant to a mean of 5.4 (SD 1.7 drugs. Cure or completion was achieved in 66.1% (442 of patients; death occurred in 20.8% (139. Patients who received an aggressive regimen were less likely to die (crude hazard ratio [HR]: 0.62; 95% CI: 0.44,0.89, compared to those who did not receive such a regimen. This association held in analyses adjusted for comorbidities and indicators of severity (adjusted HR: 0.63; 95% CI: 0.43,0.93.The aggressive regimen is a robust predictor of MDR-TB treatment outcome. TB policy makers and program directors should consider this standard as they design and implement regimens for patients with drug-resistant disease. Furthermore, the aggressive regimen should be considered the standard background regimen when designing randomized trials of treatment for drug-resistant TB.

  15. Adherence to Chronic Hepatitis C Treatment Regimen: First Report From a Referral Center in Iran

    Science.gov (United States)

    Ravi, Saeedeh; Nasiri Toosi, Mohsen; Karimzadeh, Iman; Ahadi-Barzoki, Mehdi; Khalili, Hossein

    2013-01-01

    Background Various aspects of adherence to HCV treatment such as frequency, risk factors as well as causes of non-adherence, and its real role in clinical and virological outcome of the infected patients have remained largely unknown. Objectives The current study aimed to evaluate patients’ adherence to anti-HCV medications in Iran. Materials and Methods From October 2010 to March 2011, socio-demographic characteristics, features of HCV infection, clinical properties, and habitual history of 190 patients were collected. Adherence of each patient to anti-HCV medications was determined at months 1, 3, and 6 of treatment by self-reporting and pill or empty ampoule counting. Adherence to anti-HCV treatment regimen was determined based on the 80/80/80 rule. Results Adherence rate to interferon, ribavirin, or a combination of them over the first 6 months of therapy in Iranian HCV patients measured by both methods of self-reporting and pill counting were 35.4-65.8%, 46.3-56.8%, and 28.4-51.1%, respectively. Delay in receiving new prescription, financial issues, and adverse drug reactions were the most common causes of non-adherence in the patients. Adherence to ribavirin was identified as an independent predictor of achieving the end of treatment response, or sustained virological response. Conclusions The rate of adherence to interferon and ribavirin varied significantly according to the method of calculation. Over the treatment course, adherence to interferon alpha and ribavirin, each or their combination, diminished significantly. PMID:24032043

  16. [Influence of dose regimen on gentamycin nephrotoxicity in rats].

    Science.gov (United States)

    Oliveira, V C; Tejos, C R; Hosaka, E M; Andrade, S C; Araújo, M; Vattimo, M F

    2001-06-01

    The acute renal failure (ARF), that still presents a right mortality rate (50%) can be defined as an abrupt decline of the glomerular filtration, resultant of ischemic or toxicity event. The drugs nephrotoxicity is one of the most frequent cause (27%) of ARF and it is suggested that the interval of administration of the drug can interfere in this side effect, however the best administration regimen is not very well established. This study evaluated the renal function of rats that received gentamicin (100 mg/kg) in one dose or in two doses (2 x 50 mg/kg), by intraperitoneal infusion. The results obtained in this research, indicated that the single infusion of gentamicin determined smaller nephrotoxicity by the reduction of serum concentration of this drug in 24 hours, decreasing the intracellular accumulation of this gentamicin, which is one of the main cellular mechanisms of this renal injury. The single dose treatment regime, otherwise, shows advantages not only related to the nephrotoxicity effect, but also it is relevant to the cost and safety, which can be rationable factors in the administration of this drug.

  17. Polypathology, polypharmacy, medication regimen complexity and drug therapy appropriateness.

    Science.gov (United States)

    Gómez Aguirre, N; Caudevilla Martínez, A; Bellostas Muñoz, L; Crespo Avellana, M; Velilla Marco, J; Díez-Manglano, J

    Polypathological patients are usually elderly and take numerous drugs. Polypharmacy affects 85% of these individuals and is not associated with greater survival. On the contrary, polypharmacy exposes these individuals to more adverse effects, such as weight loss, falls, functional and cognitive impairment and hospitalisations. The complexity of a drug regimen covers more aspects than the simple number of drugs consumed. The galenic form, the dosage and the method for preparing the drug can impede the understanding of and compliance with prescriptions. Both polypharmacy and therapeutic complexity are associated with poorer adherence by patients. To prevent polypharmacy, reduce complexity and improve adherence, the appropriate use of drugs is needed. Proper prescribing consists of selecting drugs that have clear evidence for their use in the indication, which are appropriate for the patient's circumstances, are well tolerated and cost-effective and whose benefits outweigh the risks. To improve the drug prescription, periodic reviews of the drugs need to be conducted, especially when the patient changes doctor and during healthcare transitions. The Beers and STOPP/START (Screening Tool of Older Person's potentially inappropriate Prescriptions/Screening Tool to Alert doctors to the Right Treatment) criteria are effective tools for this improvement. Deprescription for polymedicated polypathological patients that considers their clinical circumstances, prognosis and preferences can contribute to a more appropriate use of drugs. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  18. Population-based evaluation of the effectiveness of two regimens for emergency contraception.

    Science.gov (United States)

    Leung, Vivian W Y; Soon, Judith A; Lynd, Larry D; Marra, Carlo A; Levine, Marc

    2016-06-01

    To estimate and compare the effectiveness of the levonorgestrel and Yuzpe regimens for hormonal emergency contraception in routine clinical practice. A retrospective population-based study included women who accessed emergency contraceptives for immediate use prescribed by community pharmacists in British Columbia, Canada, between December 2000 and December 2002. Linked administrative healthcare data were used to discern the timings of menses, unprotected intercourse, and any pregnancy-related health services. A panel of experts evaluated the compatibility of observed pregnancies with the timing of events. The two regimens were compared with statistical adjustments for potential confounding. Among 7493 women in the cohort, 4470 (59.7%) received levonorgestrel and 3023 (40.3%) the Yuzpe regimen. There were 99 (2.2%) compatible pregnancies in the levonorgestrel group and 94 (3.1%) in the Yuzpe group (P=0.017). The estimated odds ratio for levonorgestrel compared with the Yuzpe regimen after adjusting for potential confounders was 0.64 (95% confidence interval 0.47-0.87). Against an expected pregnancy rate of approximately 5%, the relative and absolute risk reductions were 56.0% and 2.8%, respectively, for levonorgestrel and 36.7% and 1.8% for the Yuzpe regimen. The levonorgestrel regimen is more effective than the Yuzpe regimen in routine use. The data suggest that both regimens are less effective than has been observed in randomized trials. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  19. Genetic evolution of HIV in patients remaining on a stable HAART regimen despite insufficient viral suppression

    DEFF Research Database (Denmark)

    Kristiansen, Thomas B; Pedersen, Anders; Eugen-Olsen, Jesper

    2005-01-01

    Our objective was to investigate whether steadily increasing resistance levels are inevitable in the course of a failing but unchanged Highly Active Antiretroviral Therapy (HAART) regimen. Patients having an unchanged HAART regimen and a good CD4 response (100 cells/microl above nadir) despite co...

  20. Mifepristone in combination with prostaglandins for termination of 10-16 weeks' gestation: a systematic review

    NARCIS (Netherlands)

    Chen, Qiu-ju; Hou, Shu-ping; Meads, Catherine; Huang, Yong-mei; Hong, Qing-qing; Zhu, Hao-ping; Cheng, Li-nan; Mignini, L.; von Dadelszen, P.; Magee, L.; Sawchuck, D.; Gao, E.; Mol, B. W.; Oude Rengerink, K.; Zamora, J.; Fox, C.; Daniels, J.; Khan, K. S.; Thangaratinam, S.; Meads, C.

    2011-01-01

    Medical regimens using mifepristone in combination with prostaglandins have been widely available for women undergoing termination of pregnancy (TOP) at 10-16 weeks' gestation in China. We undertook a systematic review to compare different regimens of mifepristone with prostaglandins for TOP at

  1. The Adverse Effect of the 2-1-1 Regimen for Rabies PEP in Preschool Children.

    Science.gov (United States)

    Liu, Shu Qing; Tao, Xiao Yan; Yu, Peng Cheng; Jin, Chun Qiu; Yu, Hong Jie; Chen, Mei Shun; Zhu, Wu Yang

    2017-05-01

    Post-exposure prophylaxis (PEP) has proved to be the most important measure for rabies prevention and control. There is little information regarding adverse reactions to the Essen and 2-1-1 regimens in preschool children (aged 0-6). We reexamined the outcomes of 1,109 preschool children who were vaccinated using SPEEDA under the Essen regimen between January 2011 and December 2012 and 1,267 preschool children under the 2-1-1 regimen between January 2013 and December 2014. We find that, in preschool children, the febrile reaction after the first 2-dose injection in the 2-1-1 regimen was significantly higher than that induced by the first 1-dose in the Essen procedure. Thus, we recommend that the Essen regimen should still be used for rabies PEP in preschool children. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  2. The effect of a chlorhexidine regimen on de novo plaque formation.

    Science.gov (United States)

    Sekino, Satoshi; Ramberg, Per; Uzel, Naciye Guzin; Socransky, Sigmund; Lindhe, Jan

    2004-08-01

    To evaluate the effect of a pretreatment regimen that combined meticulous mechanical tooth cleaning with the daily use of chlorhexidine (rinse, gargle and tongue application) on de novo plaque formation and on the recolonization of various microbiological species in plaque and saliva during a 4-day period of no oral hygiene. Ten subjects aged 24-36 years with gingivitis were recruited. The study was designed as a double blind cross-over clinical trial including two phases. Each experimental phase comprised one preparatory period of 7 days and one plaque accumulation period of 4 days. During the preparatory period, the volunteers (i) performed meticulous mechanical tooth cleaning using toothbrush and dentifrice and (ii) were, in addition, given two sessions of professional tooth cleaning (PTC) The final PTC was delivered after bacterial sampling had been made on Day 0. In the Control group, no additional plaque control measures were included. In the Test group, the participants in addition to the mechanical measures (i) rinsed twice daily, for 60 s each time with a 0.2% chlorhexidine solution, (ii) gargled twice daily for 10 s with the chlorhexidine preparation, and finally (iii) brushed the dorsum of the tongue for 60 s, twice daily, with a 1.0% chlorhexidine gel. During the 4-day plaque accumulation period, the participants abstained from all mechanical and chemical plaque control measures. On Days 0, 1, 2 and 4 the quantity and quality of plaque formed was assessed by clinical means and by DNA probe techniques. The microbiota of the saliva was studied in samples obtained on Days 0 and 4. It was demonstrated that chlorhexidine used as a mouthrinse combined with gargling and tongue application during the preparatory period significantly retarded the amount of plaque that formed on tooth surfaces during the following 4 days of no oral hygiene. Further, the number of microorganisms present in the biofilm representing Days 0, 1 and 2 of the "plaque accumulation period

  3. Histological spectrum of pulmonary manifestations in kidney transplant recipients on sirolimus inclusive immunosuppressive regimens

    Directory of Open Access Journals (Sweden)

    Kirby Sean

    2012-03-01

    Full Text Available Abstract Background After the introduction of novel effective immunosuppressive therapies, kidney transplantation became the treatment of choice for end stage renal disease. While these new therapies lead to better graft survival, they can also cause a variety of complications. Only small series or case reports describe pulmonary pathology in renal allograft recipients on mTOR inhibitor inclusive therapies. The goal of this study was to provide a systematic review of thoracic biopsies in kidney transplant recipients for possible association between a type of immunosuppressive regimen and pulmonary complications. Methods A laboratory database search revealed 28 of 2140 renal allograft recipients (18 males and 10 females, 25 to 77 years old, mean age 53 years who required a biopsy for respiratory symptoms. The histological features were correlated with clinical findings including immunosuppressive medications. Results The incidence of neoplasia on lung biopsy was 0.4% (9 cases, which included 3 squamous cell carcinomas, 2 adenocarcinomas, 1 diffuse large B-cell lymphoma, 1 lymphomatoid granulomatosis, and 2 post transplant B-cell lymphoproliferative disorders. Diffuse parenchymal lung disease was identified in 0.4% (9 cases, and included 5 cases of pulmonary hemorrhage, 3 cases of organizing pneumonia and 1 case of pulmonary alveolar proteinosis. Five (0.2% cases showed histological features indicative of a localized infectious process. Patients on sirolimus had neoplasia less frequently than patients on other immunosuppressive combinations (12.5% vs. 58.3%, p = 0.03. Lung biopsies in 4 of 5 patients with clinically suspected sirolimus toxicity revealed pulmonary hemorrhage as the sole histological finding or in combination with other patterns. Conclusions Our study documents a spectrum of neoplastic and non-neoplastic lesions in renal allograft recipients on current immunosuppressive therapies. Sirolimus inclusive regimens are associated with

  4. An intraoperative irrigation regimen to reduce the surgical site infection rate following adolescent idiopathic scoliosis surgery

    Science.gov (United States)

    van Herwijnen, B; Evans, NR; Dare, CJ; Davies, EM

    2016-01-01

    Introduction The aim of this study was to compare the efficacy of a gentamicin antibiotic intraoperative irrigation regimen (regimen A) with a povidone-iodine intraoperative irrigation regimen (regimen B) and to evaluate the ability of adjunctive local vancomycin powder (regimen C) to reduce the surgical site infection (SSI) rate following idiopathic scoliosis correction. Methods This was a retrospective, single centre, two-surgeon cohort study of paediatric scoliosis procedures involving 118 patients under the age of 18 years who underwent correction for idiopathic scoliosis over a period of 42 months. Patients’ baseline characteristics, pseudarthrosis and rates of SSI were compared. Results Baseline characteristics were comparable in all three groups, with the exception of sex distribution. Over a quarter (27%) of patients with regimen B were male compared with 13% and 6% for regimens A and C respectively. Patients were mostly followed up for a minimum of 12 months. The SSI rate for both superficial and deep infections was higher with regimen A (26.7%) than with regimens B and C (7.0% and 6.3% respectively). The SSI rates for regimens B and C were comparable. No patients developed complications related to vancomycin toxicity, metalwork failure or pseudarthrosis. Conclusions Wound irrigation with a povidone-iodine solution reduces SSIs following adolescent idiopathic scoliosis surgery. The direct application of vancomycin powder to the wound is safe but does not reduce the SSI rate further in low risk patients. Additional studies are needed to elucidate whether it is effective at higher doses and in high risk patient groups. PMID:27087324

  5. Effect of traditional and integrative regimens on quality of life and early renal impairment in elderly patients with isolated systolic hypertension.

    Science.gov (United States)

    Li, Hao; Liu, Long-tao; Zhao, Wen-ming; Liu, Jian-gang; Yao, Ming-jiang; Han, Yong-xiang; Shen, Yan-peng; Liu, Xing-dong; Liu, Li; Wang, Xue-mei; Cai, Lin-lin; Guan, Jie

    2010-06-01

    To observe the effect of Chinese medical regimen and integrative medical regimen on quality of life and early renal impairment in elderly patients with isolated systolic hypertension (EISH). A multi-center, randomized, double-blinded controlled trail was adopted. A total of 270 cases of EISH were randomly divided into 3 groups: Chinese medicine group (CM), combination group and Western medicine group (WM). The course of treatment was 4 weeks. The clinical blood pressure, integral of quality of life (SF-36 scale), immunoglubin G (IgG), microalbumin (mALB), beta(2)-microglobulin (beta(2)-MG), transferrin (TRF) and N-acetyl-beta'-D-glucosa-minidase (NAG) in urine were determined before and after the treatment. After treatment, systolic blood pressure depressed significantly in each group (P<0.05), and the combination group was superior to CM or WM group in depressing SBP (P<0.05); in each group, integral of quality of life improved in different degree, and combination group was superior to WM group in all 8 dimensions (P<0.05). The level of mALB and beta(2)-MG in urine decreased in all groups (P<0.05), and the combination group was superior to CM group or WM group in decreasing mALB (P<0.05). Chinese medical regimen has affirmative effect in treating EISH patients, and could lower the systolic blood pressure, improve quality of life and early renal impairment of the patients, and integrative medical regimen has superiority on account of cooperation, and deserves further study.

  6. Cost-effectiveness analysis of low density lipoprotein cholesterol-lowering therapy in hypertensive patients with type 2 diabetes in Korea: single-pill regimen (amlodipine/atorvastatin versus double-pill regimen (amlodipine+atorvastatin

    Directory of Open Access Journals (Sweden)

    Ji-Hyun Park

    2015-02-01

    Full Text Available OBJECTIVES: Single-pill combination therapy (amlodipine/atorvastatin might be more effective than double-pill therapy (amlodipine+atorvastatin in patients with diabetes and concomitant hypertension requiring statin therapy. We compared the cost-effectiveness of a single-pill with that of double-pill for control of low density lipoprotein cholesterol (LDL-C levels, with the ultimate goal of cardiovascular disease prevention, in these patients using a cost-effectiveness analysis model that considered medication adherence. METHODS: Effectiveness was defined as the percentage (% attainment of target LDL-C levels (<100 mg/dL based on adherence for each therapy. Adherence was defined as compliance to medication (≥80% proportion of days covered. A systematic review of the literature was conducted to determine the proportion of patients who were adherent and target goal attainment based on adherence level. The annual medication costs were based on the adherence levels for each regimen. The average cost-effectiveness ratio (ACER was calculated as the cost per % attainment of the target LDL-C level. RESULTS: The ACER for the single-pill regimen was lower than for the double-pill regimen (4,123 vs. 6,062 Korean won per 1% achievement of target goal. Compared with the double-pill, the medication costs were approximately 32% lower with the single-pill. CONCLUSION:A single-pill for reductions in LDL-C is cost-effective compared with double-pill in hypertensive patients with type 2 diabetes.

  7. Cluster-Randomized Non-Inferiority Trial to Compare Supplement Consumption and Adherence to Different Dosing Regimens for Antenatal Calcium and Iron-Folic Acid Supplementation to Prevent Preeclampsia and Anaemia: Rationale and Design of the Micronutrient Initiative Study.

    Science.gov (United States)

    Omotayo, Moshood O; Dickin, Katherine L; Chapleau, Gina M; Martin, Stephanie L; Chang, Christopher; Mwanga, Erick O; Kung'u, Jacqueline K; Stoltzfus, Rebecca J

    2015-11-17

    To prevent pre-eclampsia in populations with insufficient dietary calcium (Ca) intake, the World Health Organisation (WHO) recommends routine Ca supplementation during antenatal care (ANC). WHO guidelines suggest a complex dosing regimen, requiring as many as 5 pill-taking events per day when combined with iron and folic acid (IFA) supplements. Poor adherence may undermine public health effectiveness, so simpler regimens may be preferable. This trial will compare the effect of the WHO-recommended (higher-dose) regimen vs. a simpler, lower-dose regimen on supplement consumption and pill-taking behaviours in Kenyan ANC clients. This is a parallel, non-inferiority, cluster-randomized trial; we examined 16 primary care health facilities in Kenya, 1047 pregnant women between 16-30 weeks gestational age. Higher-dose regimen: 1.5 g elemental calcium in 3 separate doses (500 mg Ca/pill) and IFA (60 mg Fe + 400 µg folic acid) taken with evening dose. Lower-dose regimen: 1.0 g calcium in 2 separate doses (500 mg Ca/pill) with IFA taken as above. Primary outcome is Ca pills consumed per day, measured by pill counts. Secondary outcomes include IFA pills consumed per day, client knowledge, motivation, social support, and satisfaction, measured at 4 to 10 weeks post-enrolment. Unit of randomization is the healthcare facility; unit of analysis is individual client. Intent-to-treat analysis will be implemented with multi-level models to account for clustering. If pregnant women prescribed lower doses of Ca ingest as many pills as women prescribed the WHO-recommended regimen, developing a lower-dose recommendation for antenatal Ca and IFA supplementation programs could save resources. Significance for public healthPre-eclampsia is a leading cause of maternal mortality. Based on clinical evidence of significant reduction in risk of pre-eclampsia, the WHO recommends including calcium (Ca) supplementation in antenatal care services in settings with inadequate dietary Ca intakes. A

  8. Colistin and Polymyxin B Dosage Regimens against Acinetobacter baumannii: Differences in Activity and the Emergence of Resistance.

    Science.gov (United States)

    Cheah, Soon-Ee; Li, Jian; Tsuji, Brian T; Forrest, Alan; Bulitta, Jürgen B; Nation, Roger L

    2016-07-01

    Infections caused by multidrug-resistant Acinetobacter baumannii are a major public health problem, and polymyxins are often the last line of therapy for recalcitrant infections by such isolates. The pharmacokinetics of the two clinically used polymyxins, polymyxin B and colistin, differ considerably, since colistin is administered as an inactive prodrug that undergoes slow conversion to colistin. However, the impact of these substantial pharmacokinetic differences on bacterial killing and resistance emergence is poorly understood. We assessed clinically relevant polymyxin B and colistin dosage regimens against one reference and three clinical A. baumannii strains in a dynamic one-compartment in vitro model. A new mechanism-based pharmacodynamic model was developed to describe and predict the drug concentrations and viable counts of the total and resistant populations. Rapid attainment of target concentrations was shown to be critical for polymyxin-induced bacterial killing. All polymyxin B regimens achieved peak concentrations of at least 1 mg/liter within 1 h and caused ≥4 log10 killing at 1 h. In contrast, the slow rise of colistin concentrations to 3 mg/liter over 48 h resulted in markedly reduced bacterial killing. A significant (4 to 6 log10 CFU/ml) amplification of resistant bacterial populations was common to all dosage regimens. The developed mechanism-based model explained the observed bacterial killing, regrowth, and resistance. The model also implicated adaptive polymyxin resistance as a key driver of bacterial regrowth and predicted the amplification of preexisting, highly polymyxin-resistant bacterial populations following polymyxin treatment. Antibiotic combination therapies seem the most promising option for minimizing the emergence of polymyxin resistance. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  9. Comparison of three different iodine-based bowel regimens for CT colonography

    Energy Technology Data Exchange (ETDEWEB)

    Campanella, Delia; Regge, Daniele [Institute for Cancer Research and Treatment, Radiology Unit, Candiolo (Italy); Morra, Lia; Delsanto, Silvia; Bert, Alberto [im3D S.p.A., Turin (Italy); Tartaglia, Vincenzo [Presidio Ospedaliero Riunito Cirie, ASL 4 Torino, Cirie (Italy); Asnaghi, Roberto [Istituto Scientifico di Veruno, Radiologia, Fondazione Salvatore Maugeri, IRCCS, Veruno, NO (Italy); Neri, Emanuele [University of Pisa, Diagnostic and Interventional Radiology, Pisa (Italy)

    2010-02-15

    The aim of this study was to compare the computed tomographic colonography (CTC) image quality and patient acceptance of three iodine-based faecal tagging bowel preparations in 60 patients undergoing the following regimens: a 2-day regimen of meal-time administration of iodine and phospho-soda (GFPH); a 2-day regimen of meal-time mild laxative, followed by iodine administered 2 h before CTC (SD); and a 2-day regimen of meal-time administration of iodine (GF). Two independent radiologists assessed tagging quality; quantitative measures included the tagged stool density, and computer-aided detection (CAD) false-positive rate. The GFPH and SD regimens provided better subjective quality than GF (p < 0.001). The latter regimen resulted in a higher proportion of insufficiently tagged segments: the measured average stool density was less than 200 HU in 10.7% in all segments vs 3.6% for SD and <0.5% for GFPH, respectively. Insufficient tagging occurred mostly in the ascending colon and the caecum. The CAD false-positive rate increased following the trend: GFPH < SD < GF (p = 0.00012). GFPH was worse tolerated than SD (p < 0.05). Considering preparation quality alone, GFPH was the best regimen, but SD provided the best balance between bowel preparation quality and patient acceptability. (orig.)

  10. Second and third responses to the same induction regimen in relapsing patients with multiple myeloma.

    Science.gov (United States)

    Paccagnella, A; Chiarion-Sileni, V; Soesan, M; Baggio, G; Bolzonella, S; De Besi, P; Casara, D; Frizzarin, M; Salvagno, L; Favaretto, A

    1991-09-01

    From September 1975 to December 1986, 115 consecutive previously untreated patients with multiple myeloma (MM) were treated with combination chemotherapy consisting of BCNU, cyclophosphamide, melphalan, vincristine, and prednisone (M-2). No patients were excluded or lost during follow-up. Forty-three percent of the patients were Stage I plus II, and 57% were Stage III. Thirty-eight patients (33%) had blood urea nitrogen greater than or equal to 40 mg/dl (substage B). Reaching an objective response treatment was stopped, generally after 1 year, and restarted at relapse. After induction therapy, 94 patients (82%) responded and had a median duration of response (MDR) of 22 months. After first relapse, 26 of 38 patients (69%) responded again to the same regimen and had an MDR of 11 months. This response rate and MDR are significantly lower than the ones achieved in induction chemotherapy. After second relapse, 7 of 16 patients (44%) again responded with an MDR of 3.5 months. The median survival time (MST) was 50.5 months for all patients. The most relevant side effect was leukopenia. No case of secondary leukemia was noticed. The authors conclude that patients with MM can be treated safely without maintenance therapy after reaching remission because a high response rate can be obtained in first and even second relapse. The planned treatment pause at remission does not adversely affect the survival time. Secondary leukemia is infrequent after this policy. Quality of life improves during the treatment pause.

  11. BRUCELLOSIS: REVIEW OF CLINICAL AND LABORATORY FEATURES AND THERAPEUTIC REGIMENS IN 44 CHILDREN

    Directory of Open Access Journals (Sweden)

    S Afsharpaiman

    2008-12-01

    Full Text Available "nBrucellosis is not uncommon in children in endemic areas. We described clinical and laboratory features and therapeutic regimens for brucellosis in children under 14 who admitted in the Pediatric Medical Center Hospital, Tehran, Iran from March 1988 until February 2001. The male: female ratio was 2:1. Family history of brucellosis and consumption of un-pasteurized milk and dairy products was positive in 20.4% and 65.9%, respectively. The common clinical findings were arthritis (79.5%, fever (77.4%, anorexia (61.4%, sweating (52.3%, splenomegaly (43.2%, hepatomegaly (34.1% and lymphadenopathy (13.65. Anemia, leukopenia and thrombocytopenia were recorded in 56.8%, 31.8% and 9.1%, respectively. Out of all patients, seropositivity rate for brucellosis was found in 97.7% using serum agglutination test. Culture of blood and bone marrow specimen were positive in 30% and 50% of samples obtained, respectively. Rifampin and co-trimoxazole were the most commonly used combination in 68.1%. The overall relapse rate was 13.6%. Arthritis and fever were the most common clinical findings of brucellosis. Wright test is a very sensitive method to detect brucella infection. Public education and control measures should be applied to prevent the zoonotic and human brucellosis. 

  12. Effects of In Vitro Antibiotic Resistance on Treatment: Bismuth-Containing Regimens

    Directory of Open Access Journals (Sweden)

    Naoki Chiba

    2000-01-01

    Full Text Available Bismuth compounds remain useful for Helicobacter pylori eradication therapy. These include colloidal bismuth subcitrate (CBS, bismuth subsalicylate (BSS and, most recently, ranitidine bismuth citrate (RBC. CBS appears to prevent the development of imidazole resistance when coadministered with nitroimidazoles. Traditional triple therapy with bismuth, metronidazole and tetracycline or amoxicillin (BMT/A only partially overcomes metronidazole resistance. However, the addition of a PPI to bismuth triple therapy largely overcomes established metronidazole resistance if treatment is given for at least one week or more. When RBC rather than PPI is used with clarithromycin, this dual regimen appears to be more effective in preventing the development of secondary clarithromycin resistance. The triple combination of RBC, metronidazole and clarithromycin appears to be effective against metronidazole resistant strains of H pylori. Thus, overall, there is some evidence that bismuth compounds may prevent the development of antibiotic resistance and that existing antibiotic resistance may at least be partially overcome in vitro and in vivo. With the growing emergence of H pylori resistance to metronidazole and clarithromycin, further research to clarify the role of bismuth compounds is required.

  13. International Organization of Standardization (ISO) and Cambridge Filter Test (CFT) Smoking Regimen Data Comparisons in Tobacco Product Marketing Applications.

    Science.gov (United States)

    Chae, Changyu; Walters, Matthew J; Holman, Matthew R

    2017-07-01

    We investigated the differences in TNCO (tar, nicotine, and carbon monoxide) smoke yields generated under the International Organization of Standardization (ISO) and Federal Trade Commission (FTC) Cambridge Filter Test (CFT) smoking regimens. Twenty-nine commercial cigarette products from the US marketplace were acquired in 2015 and tested by measuring the TNCO smoke yields generated under these 2 nonintense smoking regimens. Data obtained demonstrated a linear relationship between the TNCO yields produced under the 2 smoking regimens (R 2 > 0.99). TNCO yields produced by each product were higher under the CFT smoking regimen than the ISO smoking regimen. We found that tar, nicotine, and carbon monoxide yields were consistently 10% to 13% higher under the CFT smoking regimen than under the ISO smoking regimen. This strong correlation indicates that the 2 smoking regimens can be used to apply a correlation correction to CFT TNCO data and allow its comparison to ISO TNCO data in tobacco product marketing applications.

  14. Economic evaluation of a shortened standardised treatment regimen of antituberculosis drugs for patients with multidrug-resistant tuberculosis (STREAM): study protocol.

    Science.gov (United States)

    Gama, Elvis; Madan, Jason; Langley, Ivor; Girma, Mamo; Evans, Denise; Rosen, Sydney; Squire, S Bertel

    2016-10-17

    Multidrug-resistant tuberculosis (MDR-TB) poses a serious financial challenge to health systems and patients. The current treatment for patients with MDR-TB takes up to 24 months to complete. Evidence for a shorter regimen which differs from the standard WHO recommended MDR-TB regimen and typically lasts between 9 and 12 months has been reported from Bangladesh. This evaluation aims to assess the economic impact of a shortened regimen on patients and health systems. This evaluation is innovative as it combines patient and health system costs, as well as operational modelling in assessing the impact. An economic evaluation nested in a clinical trial with 2 arms will be performed at 4 facilities. The primary outcome measure is incremental cost to the health system of the study regimen compared with the control regimen. Secondary outcome measures are mean incremental costs incurred by patients by treatment outcome; patient costs by category (direct medical costs, transport, food and accommodation costs, and cost of guardians/accompanying persons and lost time); health systems cost by category and drugs; and costs related to serious adverse events. The study has been evaluated and approved by the Ethics Advisory Group of the International Union Against Tuberculosis and Lung Disease; South African Medical Research Ethics Committee; Wits Health Consortium Protocol Review Committee; University of the Witwatersrand Human Research Ethics Committee; University of Kwazulu-Natal Biomedical Research Ethics Committee; St Peter TB Specialized Hospital Ethical Review Committee; AHRI-ALERT Ethical Review Committee, and all participants will provide written informed consent. The results of the economic evaluation will be published in a peer-reviewed journal. ISRCTN78372190. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  15. High rates of regimen change due to drug toxicity among a cohort of South Indian adults with HIV infection initiated on generic, first-line antiretroviral treatment.

    Science.gov (United States)

    Sivadasan, Ajith; Abraham, O C; Rupali, Priscilla; Pulimood, Susanne A; Rajan, Joyce; Rajkumar, S; Zachariah, Anand; Kannangai, Rajesh; Kandathil, Abraham Joseph; Sridharan, G; Mathai, Dilip

    2009-05-01

    To determine the rates, reasons and predictors of treatment change of the initial antiretroviral treatment (ART) regimen in HIV-infected south Indian adults. In this prospective cohort study, ART-naive adults initiated on generic, fixed dose combination ART as per the National AIDS Control Organization guidelines were followed up at an academic medical center. Treatment change was defined as any event which necessitated a change in or discontinuation of the initial ART regimen. Two hundred and thirty persons with HIV infection (males 74.8% and median age 37 years) were followed up for median duration of 48 weeks. The majority (98.7%) had acquired HIV infection through the heterosexual route. Most (70.4%) had advanced IV infection (WHO clinical stage 3 or 4) and 78% had CD4+ T-lymphocyte counts below 200 cells/microL. The initial ART regimens used were: Lamivudine (3TC) with Stavudine (d4T) (in 76%) or Azidothymidine (AZT) and Nevirapine (NVP) (in 86%) or Efavirenz (EFV). The cumulative incidence of treatment change was 39.6% (91 patients). Drug toxicity (WHO grade 3 or 4) was the reason for treatment change among 62 (27%) (incidence rate 35.9/100 person-years). The most common toxicities were attributable to the thymidine analogue nucleoside reverse transcriptase inhibitors (NRTIs), d4T and AZT [lactic acidosis (8.7%), anemia (7%) and peripheral neuropathy (5.2%)]. The other toxicities were rash (3.9%) and hepatitis (1.3%) due to NVP. The mortality (4.6/100 person-years) and disease progression rates (4.1/100 person-years) were low. The ART regimens used in this study were effective in decreasing disease progression and death. However, they were associated with high rates of drug toxicities, particularly those attributable to thymidine analogue NRTI. As efforts are made to improve access to ART, treatment regimens chosen should not only be potent, but also safe.

  16. Toward a noncytotoxic glioblastoma therapy: blocking MCP-1 with the MTZ Regimen

    Directory of Open Access Journals (Sweden)

    Salacz ME

    2016-04-01

    Full Text Available Michael E Salacz,1,2 Richard E Kast,3 Najmaldin Saki,4 Ansgar Brüning,5 Georg Karpel-Massler,6 Marc-Eric Halatsch6 1Department of Internal Medicine, 2Department of Neurosurgery, University of Kansas, Kansas City, KS, USA; 3IIAIGC Study Center, Burlington, VT, USA; 4Health Research Institute, Research Center of Thalassemia and Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 5Molecular Biology Laboratory, University Hospital Munich, Munich, Germany; 6Department of Neurosurgery, University of Ulm, Ulm, Germany Abstract: To improve the prognosis of glioblastoma, we developed an adjuvant treatment directed to a neglected aspect of glioblastoma growth, the contribution of nonmalignant monocyte lineage cells (MLCs (monocyte, macrophage, microglia, dendritic cells that infiltrated a main tumor mass. These nonmalignant cells contribute to glioblastoma growth and tumor homeostasis. MLCs comprise of approximately 10%–30% of glioblastoma by volume. After integration into the tumor mass, these become polarized toward an M2 immunosuppressive, pro-angiogenic phenotype that promotes continued tumor growth. Glioblastoma cells initiate and promote this process by synthesizing 13 kDa MCP-1 that attracts circulating monocytes to the tumor. Infiltrating monocytes, after polarizing toward an M2 phenotype, synthesize more MCP-1, forming an amplification loop. Three noncytotoxic drugs, an antibiotic – minocycline, an antihypertensive drug – telmisartan, and a bisphosphonate – zoledronic acid, have ancillary attributes of MCP-1 synthesis inhibition and could be re-purposed, singly or in combination, to inhibit or reverse MLC-mediated immunosuppression, angiogenesis, and other growth-enhancing aspects. Minocycline, telmisartan, and zoledronic acid – the MTZ Regimen – have low-toxicity profiles and could be added to standard radiotherapy and temozolomide. Re-purposing older drugs has advantages of established safety and low

  17. Dose Response for Radiation Cataractogenesis: A Meta-Regression of Hematopoietic Stem Cell Transplantation Regimens

    Energy Technology Data Exchange (ETDEWEB)

    Hall, Matthew D. [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Schultheiss, Timothy E., E-mail: schultheiss@coh.org [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Smith, David D. [Division of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Nguyen, Khanh H. [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Department of Radiation Oncology, Bayhealth Cancer Center, Dover, Delaware (United States); Wong, Jeffrey Y.C. [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States)

    2015-01-01

    Purpose/Objective(s): To perform a meta-regression on published data and to model the 5-year probability of cataract development after hematopoietic stem cell transplantation (HSCT) with and without total body irradiation (TBI). Methods and Materials: Eligible studies reporting cataract incidence after HSCT with TBI were identified by a PubMed search. Seventeen publications provided complete information on radiation dose schedule, fractionation, dose rate, and actuarial cataract incidence. Chemotherapy-only regimens were included as zero radiation dose regimens. Multivariate meta-regression with a weighted generalized linear model was used to model the 5-year cataract incidence and contributory factors. Results: Data from 1386 patients in 21 series were included for analysis. TBI was administered to a total dose of 0 to 15.75 Gy with single or fractionated schedules with a dose rate of 0.04 to 0.16 Gy/min. Factors significantly associated with 5-year cataract incidence were dose, dose times dose per fraction (D•dpf), pediatric versus adult status, and the absence of an ophthalmologist as an author. Dose rate, graft versus host disease, steroid use, hyperfractionation, and number of fractions were not significant. Five-fold internal cross-validation showed a model validity of 83% ± 8%. Regression diagnostics showed no evidence of lack-of-fit and no patterns in the studentized residuals. The α/β ratio from the linear quadratic model, estimated as the ratio of the coefficients for dose and D•dpf, was 0.76 Gy (95% confidence interval [CI], 0.05-1.55). The odds ratio for pediatric patients was 2.8 (95% CI, 1.7-4.6) relative to adults. Conclusions: Dose, D•dpf, pediatric status, and regimented follow-up care by an ophthalmologist were predictive of 5-year cataract incidence after HSCT. The low α/β ratio indicates the importance of fractionation in reducing cataracts. Dose rate effects have been observed in single institution studies but not in the

  18. A cost comparison of alternative regimens for treatment-refractory partial seizure disorder: an econometric analysis.

    Science.gov (United States)

    Lee, Won Chan; Hoffmann, Marc S; Arcona, Steve; D'Souza, Joseph; Wang, Qin; Pashos, Chris L

    2005-10-01

    Partial seizure disorder is typically treated by monotherapy with antiepileptic drugs (AEDs). However, when the condition is refractory to the initial treatment regimen, patients may be switched to monotherapy with another AED or to combination therapy with the initial AED plus a second AED. The purpose of this study was to examine the economic costs associated with treatment-refractory partial seizure disorder and to compare the costs of 2 alternative approaches: a switch to oxcarbazepine (OXC) monotherapy or the addition to the regimen of another AED (AED add-on). Adult patients with a diagnosis of partial seizure disorder who received initial AED monotherapy between January 1, 2000, and March 31, 2003, were identified from the PharMetrics Patient-Centric Database, a health plan administrative claims database. The medical and pharmacy history of these patients was analyzed from 6 months before a change to either OXC monotherapy or AED add-on therapy through 12 months after the change in treatment. Total health care resource utilization and the associated costs were compared within each cohort before and after the change, as well as between cohorts, with statistical differences tested using Wilcoxon rank sum tests. Multivariate econometric analyses were performed to examine the impact of age, sex, geographic location, Charlson Comorbidity Index, and the presence of specific comorbidities. Demographic and clinical characteristics 102 were similar between the OXC monotherapy cohort (n = 259) and the AED add-on cohort (n = 795). Annual direct treatment costs increased in both groups in the period after the failure of initial monotherapy, increasing from 10,462 US dollars to 11,360 US dollars in the OXC cohort and from 10,137 US dollars to 12,201 US dollars in the AED add on cohort (P < 0.01). Increased pharmacy costs were the primary driver behind cost increases in both cohorts. Patients in the AED add-on cohort were significantly more likely to have an emergency

  19. Priority-Setting for Novel Drug Regimens to Treat Tuberculosis: An Epidemiologic Model.

    Directory of Open Access Journals (Sweden)

    Emily A Kendall

    2017-01-01

    Full Text Available Novel drug regimens are needed for tuberculosis (TB treatment. New regimens aim to improve on characteristics such as duration, efficacy, and safety profile, but no single regimen is likely to be ideal in all respects. By linking these regimen characteristics to a novel regimen's ability to reduce TB incidence and mortality, we sought to prioritize regimen characteristics from a population-level perspective.We developed a dynamic transmission model of multi-strain TB epidemics in hypothetical populations reflective of the epidemiological situations in India (primary analysis, South Africa, the Philippines, and Brazil. We modeled the introduction of various novel rifampicin-susceptible (RS or rifampicin-resistant (RR TB regimens that differed on six characteristics, identified in consultation with a team of global experts: (1 efficacy, (2 duration, (3 ease of adherence, (4 medical contraindications, (5 barrier to resistance, and (6 baseline prevalence of resistance to the novel regimen. We compared scale-up of these regimens to a baseline reflective of continued standard of care. For our primary analysis situated in India, our model generated baseline TB incidence and mortality of 157 (95% uncertainty range [UR]: 113-187 and 16 (95% UR: 9-23 per 100,000 per year at the time of novel regimen introduction and RR TB incidence and mortality of 6 (95% UR: 4-10 and 0.6 (95% UR: 0.3-1.1 per 100,000 per year. An optimal RS TB regimen was projected to reduce 10-y TB incidence and mortality in the India-like scenario by 12% (95% UR: 6%-20% and 11% (95% UR: 6%-20%, respectively, compared to current-care projections. An optimal RR TB regimen reduced RR TB incidence by an estimated 32% (95% UR: 18%-46% and RR TB mortality by 30% (95% UR: 18%-44%. Efficacy was the greatest determinant of impact; compared to a novel regimen meeting all minimal targets only, increasing RS TB treatment efficacy from 94% to 99% reduced TB mortality by 6% (95% UR: 1%-13%, half the

  20. Priority-Setting for Novel Drug Regimens to Treat Tuberculosis: An Epidemiologic Model.

    Science.gov (United States)

    Kendall, Emily A; Shrestha, Sourya; Cohen, Ted; Nuermberger, Eric; Dooley, Kelly E; Gonzalez-Angulo, Lice; Churchyard, Gavin J; Nahid, Payam; Rich, Michael L; Bansbach, Cathy; Forissier, Thomas; Lienhardt, Christian; Dowdy, David W

    2017-01-01

    Novel drug regimens are needed for tuberculosis (TB) treatment. New regimens aim to improve on characteristics such as duration, efficacy, and safety profile, but no single regimen is likely to be ideal in all respects. By linking these regimen characteristics to a novel regimen's ability to reduce TB incidence and mortality, we sought to prioritize regimen characteristics from a population-level perspective. We developed a dynamic transmission model of multi-strain TB epidemics in hypothetical populations reflective of the epidemiological situations in India (primary analysis), South Africa, the Philippines, and Brazil. We modeled the introduction of various novel rifampicin-susceptible (RS) or rifampicin-resistant (RR) TB regimens that differed on six characteristics, identified in consultation with a team of global experts: (1) efficacy, (2) duration, (3) ease of adherence, (4) medical contraindications, (5) barrier to resistance, and (6) baseline prevalence of resistance to the novel regimen. We compared scale-up of these regimens to a baseline reflective of continued standard of care. For our primary analysis situated in India, our model generated baseline TB incidence and mortality of 157 (95% uncertainty range [UR]: 113-187) and 16 (95% UR: 9-23) per 100,000 per year at the time of novel regimen introduction and RR TB incidence and mortality of 6 (95% UR: 4-10) and 0.6 (95% UR: 0.3-1.1) per 100,000 per year. An optimal RS TB regimen was projected to reduce 10-y TB incidence and mortality in the India-like scenario by 12% (95% UR: 6%-20%) and 11% (95% UR: 6%-20%), respectively, compared to current-care projections. An optimal RR TB regimen reduced RR TB incidence by an estimated 32% (95% UR: 18%-46%) and RR TB mortality by 30% (95% UR: 18%-44%). Efficacy was the greatest determinant of impact; compared to a novel regimen meeting all minimal targets only, increasing RS TB treatment efficacy from 94% to 99% reduced TB mortality by 6% (95% UR: 1%-13%, half the

  1. Primary radiotherapy of stage IIA/B-IIIB cervical carcinoma. A comparison of continuous versus sequential regimens

    International Nuclear Information System (INIS)

    Mayer, A.; Nemeskeri, C.; Petnehazi, C.; Varga, S.; Naszaly, A.; Borgulya, G.

    2004-01-01

    fraction of HDR-BT in the SRT regimen was obviously too high. To achieve a significant improvement in local control and disease-free survival (DFS) as well as overall survival (OS), the combination with modern chemotherapy regimens and regional deep hyperthermia may rather be the treatment option. (orig.)

  2. Primary radiotherapy of stage IIA/B-IIIB cervical carcinoma. A comparison of continuous versus sequential regimens

    Energy Technology Data Exchange (ETDEWEB)

    Mayer, A.; Nemeskeri, C.; Petnehazi, C.; Varga, S.; Naszaly, A. [Center of Oncoradiology, Uzsoki Hospital, Budapest (Hungary); Borgulya, G. [National Pediatric Cancer Registry of the Hungarian Pediatric Oncology Working Group, 2nd Dept. of Pediatrics, Semmelweis Univ. Budapest (Hungary)

    2004-04-01

    fraction of HDR-BT in the SRT regimen was obviously too high. To achieve a significant improvement in local control and disease-free survival (DFS) as well as overall survival (OS), the combination with modern chemotherapy regimens and regional deep hyperthermia may rather be the treatment option. (orig.)

  3. A viral dynamic model for treatment regimens with direct-acting antivirals for chronic hepatitis C infection.

    Directory of Open Access Journals (Sweden)

    Bambang S Adiwijaya

    2012-01-01

    Full Text Available We propose an integrative, mechanistic model that integrates in vitro virology data, pharmacokinetics, and viral response to a combination regimen of a direct-acting antiviral (telaprevir, an HCV NS3-4A protease inhibitor and peginterferon alfa-2a/ribavirin (PR in patients with genotype 1 chronic hepatitis C (CHC. This model, which was parameterized with on-treatment data from early phase clinical studies in treatment-naïve patients, prospectively predicted sustained virologic response (SVR rates that were comparable to observed rates in subsequent clinical trials of regimens with different treatment durations in treatment-naïve and treatment-experienced populations. The model explains the clinically-observed responses, taking into account the IC50, fitness, and prevalence prior to treatment of viral resistant variants and patient diversity in treatment responses, which result in different eradication times of each variant. The proposed model provides a framework to optimize treatment strategies and to integrate multifaceted mechanistic information and give insight into novel CHC treatments that include direct-acting antiviral agents.

  4. Medication Regimen Complexity and Polypharmacy as Factors Associated With All-Cause Mortality in Older People

    Science.gov (United States)

    Wimmer, Barbara C.; Bell, J. Simon; Fastbom, Johan; Wiese, Michael D.; Johnell, Kristina

    2016-01-01

    Objectives: To investigate whether medication regimen complexity and/or polypharmacy are associated with all-cause mortality in older people. Methods: This was a population-based cohort study among community-dwelling and institutionalized people ≥60 years old (n = 3348). Medication regimen complexity was assessed using the 65-item Medication Regimen Complexity Index (MRCI) in 10-unit steps. Polypharmacy was assessed as a continuous variable (number of medications). Mortality data were obtained from the Swedish National Cause of Death Register. Cox proportional hazard models were used to compute unadjusted and adjusted hazard ratios (HRs) and 95% CIs for the association between regimen complexity and polypharmacy with all-cause mortality over a 3-year period. Subanalyses were performed stratifying by age (≤80 and>80 years), sex, and cognition (Mini-Mental State Examination [MMSE] 80 years old or with MMSE 80 years old, or in those with MMSE<26. These different associations with mortality deserve further investigation. PMID:26681444

  5. Fewer Doses of HPV Vaccine Result in Immune Response Similar to Three-Dose Regimen

    Science.gov (United States)

    ... Note Fewer doses of HPV vaccine result in immune response similar to three-dose regimen Posted: November 4, ... or three doses of Cervarix. They also measured immune responses of unvaccinated women who, at enrollment, were found ...

  6. Solidified self-nanoemulsifying formulation for oral delivery of combinatorial therapeutic regimen

    DEFF Research Database (Denmark)

    Jain, Amit K; Thanki, Kaushik; Jain, Sanyog

    2014-01-01

    PURPOSE: The present work reports rationalized development and characterization of solidified self-nanoemulsifying drug delivery system for oral delivery of combinatorial (tamoxifen and quercetin) therapeutic regimen. METHODS: Suitable oil for the preparation of liquid SNEDDS was selected based o...

  7. Busulfan, Fludarabine, and Thiotepa Conditioning Regimen for Non Malignant Disease

    Science.gov (United States)

    2018-04-19

    Bone Marrow Failure Syndrome; Thalassemia; Sickle Cell Disease; Diamond Blackfan Anemia; Acquired Neutropenia in Newborn; Acquired Anemia Hemolytic; Acquired Thrombocytopenia; Hemophagocytic Lymphohistiocytoses; Wiskott-Aldrich Syndrome; Chronic Granulomatous Disease; Common Variable Immunodeficiency; X-linked Lymphoproliferative Disease; Severe Combined Immunodeficiency; Hurler Syndrome; Mannosidosis; Adrenoleukodystrophy

  8. Choosing an effective and affordable antibiotic regimen for sexually ...

    African Journals Online (AJOL)

    For patients with urethritis, trimethoprim 320 mg/sulfamethoxazole 1600 mg PO for 2 days (TMPSMX), or the combination of amoxicillin 3 gm, probenecid 1 gm, and clavulanate 125 mg PO once (APC), failed to cure gonorrhoea effectively. Amoxicillin 3 gm, and clavulanate 125 mg, PO once with doxycycline 100 mg BID for 7 ...

  9. High efficacy of short-term quinine-antibiotic combinations for treating adult malaria patients in an area in which malaria is hyperendemic.

    OpenAIRE

    Metzger, W; Mordmüller, B; Graninger, W; Bienzle, U; Kremsner, P G

    1995-01-01

    In a randomized trial, a three-dose quinine monotherapy was compared with short-term combination regimens of quinine-clindamycin and quinine-doxycycline for treating adult Gabonese patients with Plasmodium falciparum malaria. In quinine-treated patients, only 38% were ultimately cured. In contrast, more than 90% of patients were cured after treatment with either combination regimen.

  10. Leveraging protein binding and the EPR effect in legacy chemotherapy regimens

    Directory of Open Access Journals (Sweden)

    Shireesh Apte

    2016-12-01

    Full Text Available Legacy chemotherapy regimens have the potential to be significantly more effective and less toxic if the dosage is titrated so that the mole ratio of drugs to circulating albumin is less than or equal to 1 and the order of administration of the drugs within each course of the regimen follows the sequence most hydrophobic (usually the least dose to least hydrophobic (usually the largest dose

  11. Interferon free hepatitis C treatment regimens: the beginning of another era.

    Science.gov (United States)

    Poordad, Fred; Chee, Grace M

    2012-02-01

    Hepatitis C is a virus affecting millions worldwide and is a major health risk. With the potentially severe adverse event profile of the current backbone of therapy, interferon, there is an impetus to discover interferon free treatment regimens. With the development of new oral direct acting antivirals, interferon free regimens may be available in the next few years. This article discusses some of the preliminary data from interferon free studies.

  12. Dietary regimens of athletes competing at the Delhi 2010 Commonwealth Games.

    Science.gov (United States)

    Pelly, Fiona E; Burkhart, Sarah J

    2014-02-01

    The aim of this study was to investigate the dietary regimens reported by athletes competing at a major international competition and report whether these were based on nutrient composition, religious beliefs, cultural eating style, food intolerance or avoidance of certain ingredients. A questionnaire was randomly distributed to 351 athletes in the main dining hall of the athletes' village over the three main meal periods during the Delhi 2010 Commonwealth Games (23rd Sept-14th Oct, 2010). The majority (n = 218, 62%) of athletes reported following one or more dietary regimens, with 50% (n = 174) following a diet based on the nutrient composition of the food. Significantly more athletes from weight category and aesthetic sports (28%, p = .005) and from power/sprint sports (41%, p = .004) followed low fat and high protein regimens respectively. Other specialized dietary regimens were followed by 33% of participants, with avoidance of red meat (13%), vegetarian (7%), Halal (6%), and low lactose regimens (5%) reported most frequently. Significantly more athletes from non-Western regions followed a vegetarian diet (p < .001), while more vegetarians reported avoiding additives (p = .013) and wheat (p ≤ .001). A Western style of eating was the most commonly reported cultural regimen (72% of total with 23% from non-Western regions). Those following a Western diet were significantly more likely to report following a regimen based on nutrient composition (p = .02). As a high proportion of athletes from differing countries and sports follow specialized dietary regimens, caterers and organizers should ensure that adequate nutrition support and food items are available at similar events.

  13. Anticoagulation Regimens During Pregnancy in Patients With Mechanical Heart Valves: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Xu, Zhe; Fan, Jin; Luo, Xin; Zhang, Wen-Bo; Ma, Jun; Lin, Yu-Bi; Ma, Shao-Hong; Chen, Xin; Wang, Zhi-Ping; Ou, Jing-Song; Zhang, Xi

    2016-10-01

    Managing anticoagulation in pregnant women with mechanical heart valves remains challenging. Our aim was to evaluate the effectiveness and safety of 4 regimens in these women. Relevant studies published before June 2015 were collected in several databases and analyzed with RevMan version 5.3 and SPSS version 19.0. Four regimens were defined as follows: a regimen of a vitamin K antagonist (VKA) throughout pregnancy; a heparin (H)/VKA regimen using VKAs except for unfractionated heparin (UFH) or low molecular weight heparin (LMWH) during 6-12 weeks of pregnancy; a LMWH regimen of adjusted LMWH doses throughout pregnancy; and a UFH regimen of adjusted UFH doses throughout pregnancy. The low warfarin dose in the VKA regimen was defined as 5 mg/d or less. Fifty-one studies comprising 2113 pregnancies in 1538 women were included. The rate of fetal wastage was significantly higher in the high warfarin dose subgroup than in the low dose one. Compared with the H/VKA regimen, the rate of maternal major thromboembolic event in the low-dose VKA regimen group was significantly lower, although the fetal outcomes were similar. Compared with the H/VKA regimen, the rate of fetal wastage in the LMWH regimen group was significantly lower, and the maternal outcomes were similar. The UFH regimen presented the worst maternal and fetal outcomes. In the absence of large prospective trials, this meta-analysis showed that the VKA regimen should be best for pregnant women with a low warfarin dose, and the H/VKA regimen might be reasonable for those with a high warfarin dose. The LMWH regimen could be used for those who refuse VKA. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  14. The relationship between self-concept and adherence to therapeutic regimens in patients with heart failure.

    Science.gov (United States)

    Heydari, Abbas; Ahrari, Shahnaz; Vaghee, Saeed

    2011-01-01

    Cardiovascular diseases are the primary cause of death in Iran, and currently, heart failure (HF) has a prevalence of 3500 in 100,000 people. Despite advances in medical treatment for HF, nonadherence to prescribed therapeutic regimen remains as a problem among HF patients. A better understanding of the factors that influence patient adherence to therapeutic regimen may help nurses enhance quality of care in HF patients. The purpose of this study was to examine the relationship between self-concept cognitive perception (threat and challenge) and adherence to therapeutic regimens in patients with HF in an Iranian population. Using a descriptive correlational design, a convenience sample of 108 HF patients were selected from 2 major medical and academic centers, affiliated with Mashhad University of Medical Sciences in Iran. Two validated and reliable questionnaires including Cognitive Perception of Cardiovascular Healthy Lifestyles and Adherence questionnaires were completed by each patient. A direct relationship between challenge to self-concept and adherence to prescribed regimen was noted (P self-concept had an inverse relationship to adherence (P self-concept adhered more to the prescribed therapeutic regimen. Through education and counseling, nurses can empower their patients to perceive HF as a challenge to better adhere to the prescribed therapeutic regimen.

  15. Cost-effectiveness and budget impact of interferon-free direct-acting antiviral-based regimens for hepatitis C treatment: the French case.

    Science.gov (United States)

    Deuffic-Burban, S; Obach, D; Canva, V; Pol, S; Roudot-Thoraval, F; Dhumeaux, D; Mathurin, P; Yazdanpanah, Y

    2016-10-01

    We evaluated the cost-effectiveness and the budget impact of new DAA-based regimen use in France. A Markov model simulated chronic hepatitis C (CHC) treatment interventions with IFN-based and IFN-free regimens at stage of fibrosis ≥F3, ≥F2 or regardless of fibrosis stage, and treatment either with the least or the most expensive combination. It estimated quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). It also assessed the budget impact over 5 years of treating all CHC-screened patients, regardless of fibrosis, assuming ≤20 000 patients treated/year and priority to ≥F3. Sensitivity analyses were also conducted. For genotypes (G) 1-4, the initiation of IFN-free regardless of fibrosis was a cost-effective strategy compared to prior standard of care (SOC) initiated at stage F2: €40 400-88 300/QALY gained in G1; similar results were obtained for patients infected with G4. Considering G2-3, the most cost-effective strategy was IFN-based regimens regardless of fibrosis compared to prior SOC initiated at stage F2: €21 300 and €19 400/QALY gained, respectively; the strategy with IFN-free regimens being more effective but not cost-effective at current costs. The budget impact of treating all CHC-screened patients over 5 years would range between 3.5 and 7.2 billion €, depending on whether one considers the least or the most expensive combination of new DAAs and whether one treats G2-3 with IFN-based or IFN-free new DAAs. In France, treatment initiation with new DDAs regardless of fibrosis stage is cost-effective, but would add 3.5-7.2 billion € to an already overburdened medical care system. © 2016 John Wiley & Sons Ltd.

  16. Rituximab, Cyclophosphamide, Dexamethasone (RCD) regimen induces cure in WSU-WM xenograft model and a partial remission in previously treated Waldenstrom's macroglobulinemia patient.

    Science.gov (United States)

    Mohammad, Ramzi M; Aboukameel, Amro; Nabha, Sanaa; Ibrahim, Dina; Al-Katib, Ayad

    2002-08-01

    Waldenstrom's macroglobulinemia (WM) is an uncommon lymphoproliferative disease which remains incurable with current treatment protocols. We have previously established a permanent WM cell line, WSU-WM, which grows as a xenograft in severe combined immune deficient (SCID) mice. In this study, we investigated the antitumor effects of Rituximab (RTX), Cyclophosphamide (CTX), Dexamethasone (DEX) [RCD]-Regimen in vivo WSU-WM SCID xenograft and in a patient with WM. For the pre-clinical efficacy study, WSU-WM-bearing SCID mice were randomly assigned to receive RTX (150 mg/kg/inj, i.v., QDX5), CTX (90 mg/kg/inj, s.c. QDX5) as single agents or diluent. The combination group received RTX at 150 mg/kg/inj, QDX5; CTX at 150 mg/kg/inj, QODX3 and DEX at 1.0 mg/kg/inj, i.v., QDX5. Tumor growth inhibition (T/C), tumor growth delay (T - C), and log10 kill (net) for RTX and CTX were 24.5%, 37 days, 5.52 and 88%, 0.0 days, 0.0log10 kill, respectively. No cures were observed with either agent; however, all mice (6/6, with bilateral tumors) were cured when treated with RCD-regimen. A 57-year-old patient with relapsed WM was treated with the RCD-regimen and showed an excellent partial remission for seven months. The patient tolerated the treatment very well, the hemoglobin improved dramatically, platelets remained stable, the IgM level normalized and there was only minimal involvement of bone marrow. Based on these results, the RCD regimen is effective against WM and its activity should be further evaluated in clinical trials.

  17. Cluster-randomized non-inferiority trial to compare supplement consumption and adherence to different dosing regimens for antenatal calcium and iron-folic acid supplementation to prevent preeclampsia and anaemia: rationale and design of the Micronutrient Initiative study

    Directory of Open Access Journals (Sweden)

    Moshood O. Omotayo

    2015-11-01

    Full Text Available Background: To prevent pre-eclampsia in populations with insufficient dietary calcium (Ca intake, the World Health Organisation (WHO recommends routine Ca supplementation during antenatal care (ANC. WHO guidelines suggest a complex dosing regimen, requiring as many as 5 pill-taking events per day when combined with iron and folic acid (IFA supplements. Poor adherence may undermine public health effectiveness, so simpler regimens may be preferable. This trial will compare the effect of the WHO-recommended (higher-dose regimen vs. a simpler, lower-dose regimen on supplement consumption and pill-taking behaviours in Kenyan ANC clients. Design and methods: This is a parallel, non-inferiority, cluster-randomized trial; we examined 16 primary care health facilities in Kenya, 1047 pregnant women between 16-30 weeks gestational age. Higher-dose regimen: 1.5 g elemental calcium in 3 separate doses (500 mg Ca/pill and IFA (60 mg Fe + 400 μg folic acid taken with evening dose. Lower-dose regimen: 1.0 g calcium in 2 separate doses (500 mg Ca/pill with IFA taken as above. Measurements: Primary outcome is Ca pills consumed per day, measured by pill counts. Secondary outcomes include IFA pills consumed per day, client knowledge, motivation, social support, and satisfaction, measured at 4 to 10 weeks post-enrolment. Statistical analyses: Unit of randomization is the health-care facility; unit of analysis is individual client. Intent-to-treat analysis will be implemented with multi-level models to account for clustering. Expected public health impact: If pregnant women prescribed lower doses of Ca ingest as many pills as women prescribed the WHO-recommended regimen, developing a lower-dose recommendation for antenatal Ca and IFA supplementation programs could save resources.

  18. Comparison of caloric intake and weight outcomes of an ad lib feeding regimen for preterm infants in two nurseries.

    Science.gov (United States)

    Pridham, K F; Kosorok, M R; Greer, F; Kayata, S; Bhattacharya, A; Grunwald, P

    2001-09-01

    Effects on caloric intake and weight gain of an ad libitum (ad lib) feeding regimen for preterm infants may be specific to a special care nursery. To explore across two nurseries the similarity of effect on caloric intake and weight gain of an ad lib feeding regimen compared with a prescribed regimen and the similarity of effect of caloric intake on weight gain. All infants participating in the multi-site randomized clinical trial (RCT) of the ad lib feeding regimen were lib. After accounting for caloric intake, the ad lib regimen did not affect weight gain. The time-by-regimen interaction effect on caloric intake was significant in both nurseries. Caloric intake for infants fed ad lib increased significantly over 5 days. Despite differences between nurseries in infant characteristics and in protocol implementation, the feeding regimen effect was consistent for caloric intake and weight gain. Further support was found for the development of infant self-regulatory capacity.

  19. Psoriasis treatment: faster and long-standing results after bathing in geothermal seawater. A randomized trial of three UVB phototherapy regimens.

    Science.gov (United States)

    Eysteinsdóttir, Jenna Huld; Ólafsson, Jón Hjaltalín; Agnarsson, Bjarni A; Lúðvíksson, Björn Rúnar; Sigurgeirsson, Bárður

    2014-02-01

    The combination of seawater baths and narrowband ultraviolet B (NB-UVB) is a known treatment for psoriasis. This study evaluates two treatment regimens that combine bathing in geothermal seawater and NB-UVB therapy in comparison with NB-UVB monotherapy. Sixty-eight psoriasis patients were randomly assigned to outpatient bathing in geothermal seawater combined with NB-UVB therapy three times a week, intensive daily treatment involving bathing in geothermal seawater combined with NB-UVB therapy, or NB-UVB therapy alone three times a week; treatment period was 6 weeks. Disease severity [Psoriasis Area Severity Index (PASI) and Lattice System Physician's Global Assessment scores], quality of life (Dermatology Life Quality Index) and histological changes were evaluated before, during and after treatment. The primary end point was the proportion of patients who achieved PASI 75 at 6 weeks. At 6 weeks, the percentage of patients who achieved PASI 75 and PASI 90 was significantly greater for both regimens, bathing in geothermal seawater three times a week (68.1% and 18.2%, respectively) and intensive treatment with geothermal seawater (73.1% and 42.3%, respectively) than for NB-UVB monotherapy (16.7% and 0%, respectively) (P seawater combined with NB-UVB therapy in psoriasis induces faster clinical and histological improvement, produces longer remission time and permits lower NB-UVB doses than UVB therapy alone. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Metronomic oral topotecan with pazopanib is an active antiangiogenic regimen in mouse models of aggressive pediatric solid tumor.

    Science.gov (United States)

    Kumar, Sushil; Mokhtari, Reza Bayat; Sheikh, Reihaneh; Wu, Bing; Zhang, Libo; Xu, Ping; Man, Shan; Oliveira, Indhira Dias; Yeger, Herman; Kerbel, Robert S; Baruchel, Sylvain

    2011-09-01

    Low dose metronomic (LDM) chemotherapy, combined with VEGF signaling pathway inhibitors, is a highly effective strategy to coordinately inhibit angiogenesis and tumor growth in many adult preclinical cancer models. We have tested the efficacies of daily oral LDM topotecan alone and in combination with pazopanib, a VEGF receptor inhibitor, in three pediatric extracranial solid tumor mouse models. In vitro dose-response study of topotecan and pazopanib was conducted on several neuroblastoma, osteosarcoma, and rhabdomyosarcoma cell lines. In vivo antitumor efficacies of the LDM topotecan and pazopanib as single agents and in combination were tested on 4 subcutaneous xenograft models and on 2 neuroblastoma metastatic models. Circulating angiogenic factors such as circulating endothelial cells (CEC), circulating endothelial pro genitor cells (CEP), and microvessel densities were used as surrogate biomarker markers of antiangiogenic activity. In vitro, topotecan caused a dose-dependent decrease in viabilities of all cell lines, while pazopanib did not. In vivo, combination of topotecan + pazopanib (TP + PZ) showed significant antitumor activity and significant enhancement in survival compared with the respective single agents in all models. Reductions in viable CEP and/or CEC levels and tumor microvessel density were correlated with tumor response and therefore confirmed the antiangiogenic activity of the regimens. Pharmacokinetic studies of both drugs did not reveal any drug-drug interaction. Metronomic administration of TP + PZ showed a statistically significant antitumor activity compared with respective single agents in pediatric tumor mouse models and represent a valid option as a maintenance therapy in aggressive pediatric solid tumors. ©2011 AACR.

  1. Effectiveness of oral contraceptive pills in a large U.S. cohort comparing progestogen and regimen.

    Science.gov (United States)

    Dinger, Jürgen; Minh, Thai Do; Buttmann, Nina; Bardenheuer, Kristina

    2011-01-01

    To estimate real-life effectiveness of oral contraceptive pills by progestogen, length of pill-free interval, and body mass index while focusing on the effect of progestogens with a long half-life and on 24-day oral contraceptive pills regimens. Outcome data from 52,218 U.S. participants in the International Active Surveillance of Women Taking Oral Contraceptives—a large, prospective, controlled, noninterventional, long-term cohort study with active surveillance of the study participants—were used to analyze contraceptive failure in association with oral contraceptive pills use. Low loss to follow-up is ensured by a comprehensive follow-up procedure. Contraceptive failure rates are described by Pearl Index and life-table analysis. Inferential statistics for contraceptive failure are based on Cox regression models. Analyses are based on 1,634 unintended pregnancies during 73,269 woman-years of oral contraceptive pills exposure. Life-table estimates of contraceptive failure for a 24-day regimen of drospirenone and ethinyl estradiol and 21-day regimens of other progestogens were 2.1% and 3.5% after the first study year, and 4.7% and 6.7% after the third year. The adjusted hazard ratio was 0.7 (95% confidence interval 0.6–0.8). Direct comparisons of the 24-day and 21-day regimens of drospirenone and norethisterone, respectively, showed also lower contraceptive failure rates for 24-day regimens. Contraceptive failure rates adjusted for age, parity and educational level showed a slight increase with higher body mass index. The 24-day oral contraceptive regimens containing a progestogen with a long half-life show higher contraceptive effectiveness under routine medical conditions compared with conventional 21-day regimens. Obesity seems to be associated with a slight reduction of contraceptive effectiveness. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00335257. II

  2. Hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Matsuyama, Takaharu; Kato, Koji [Nagoya First Red Cross Hospital (Japan). Children' s Medical Center; Hanada, Ryoji [Saitama Children' s Medical Center, Iwatsuki (Japan)] [and others

    2002-07-01

    A multicenter comparative study was carried out to investigate the efficacy and safety of hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia. One hundred twenty three patients at a variety of remission stages were eligible for study participation. Eighty-nine were transplanted with allogeneic grafts and 34 patients with autologous grafts (23 cases with bone marrow and 11 cases with peripheral blood stem cells). Conditioning regimens used were as follows: melphalan and busulfan for 40 patients, melphalan, busulfan and TBI for 44 patients, other regimens for 39 patients. To accelerate engraftment G-CSF (lenograstim) was administered as a 1-hour or 24-hour drip infusion daily at 5 {mu}g/kg from day 5 until hematological recovery. The five year disease free survival (DFS) was 63% for 42 patients at CR1, 41% for 41 patients at CR2 and 33% for 40 patients at other stages. There was no significant difference in the DFS between allogeneic-transplantation and autologous-transplantation in all disease stages. In patients at remission stage for CR1 and CR2, the 5-year DFS by conditioning regimen was 63% for regimen with melphalan and busulfan, 54% for regimen with melphalan, busulfan and TBI and 54% for regimens with melphalan and TBI. There was no significant difference in the DFS between the groups. Serious complications such as renal failure were observed in 11%, veno-occlusive disease in 9%, and interstitial pneumonia in 9%. The most dominating cause of death was relapse in the disease (48% of deaths) which was most commonly observed in autologous transplantation. Contrary to that, treatment related toxic death was the most frequent cause of deaths in allogeneic-transplantation. (author)

  3. Hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Matsuyama, Takaharu; Kato, Koji

    2002-01-01

    A multicenter comparative study was carried out to investigate the efficacy and safety of hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia. One hundred twenty three patients at a variety of remission stages were eligible for study participation. Eighty-nine were transplanted with allogeneic grafts and 34 patients with autologous grafts (23 cases with bone marrow and 11 cases with peripheral blood stem cells). Conditioning regimens used were as follows: melphalan and busulfan for 40 patients, melphalan, busulfan and TBI for 44 patients, other regimens for 39 patients. To accelerate engraftment G-CSF (lenograstim) was administered as a 1-hour or 24-hour drip infusion daily at 5 μg/kg from day 5 until hematological recovery. The five year disease free survival (DFS) was 63% for 42 patients at CR1, 41% for 41 patients at CR2 and 33% for 40 patients at other stages. There was no significant difference in the DFS between allogeneic-transplantation and autologous-transplantation in all disease stages. In patients at remission stage for CR1 and CR2, the 5-year DFS by conditioning regimen was 63% for regimen with melphalan and busulfan, 54% for regimen with melphalan, busulfan and TBI and 54% for regimens with melphalan and TBI. There was no significant difference in the DFS between the groups. Serious complications such as renal failure were observed in 11%, veno-occlusive disease in 9%, and interstitial pneumonia in 9%. The most dominating cause of death was relapse in the disease (48% of deaths) which was most commonly observed in autologous transplantation. Contrary to that, treatment related toxic death was the most frequent cause of deaths in allogeneic-transplantation. (author)

  4. A dosing regimen for immediate N-acetylcysteine treatment for acute paracetamol overdose.

    Science.gov (United States)

    Shen, Finna; Coulter, Carolyn V; Isbister, Geoffrey K; Duffull, Stephen B

    2011-08-01

    Current treatment of paracetamol (acetaminophen) poisoning involves initiating a 3-phase N-acetylcysteine (NAC) infusion after comparing a plasma concentration, taken ≥ 4 h post-overdose, to a nomogram. This may result in dosing errors, a delay in treatment, or possibly more adverse effects - due to the use of a high dose rate for the first infusion when treatment is initiated. Our aim was to investigate a novel dosing regimen for the immediate administration of NAC on admission at a lower infusion rate. We used a published population pharmacokinetic model of NAC to simulate a scenario where a patient presents to the hospital 2 h post-overdose. The conventional regimen is commenced 6 h post-overdose when the 4-h plasma paracetamol concentration is available. We investigated an NAC infusion using a lower dosing rate initiated immediately on presentation. We determined a dosing rate that gave an area under the curve (AUC) of the concentration-time curve that was the same or greater than that from the conventional regimen on 90% of occasions. Lower dosing rates of NAC initiated immediately resulted in a similar exposure to NAC. An infusion of 110 mg/kg over the first 5 h (22 mg/kg/h) followed by the last two phases of the conventional regimen, or 200 mg/kg over 9 h (22.6 mg/kg/h) followed by the last phase of the conventional regimen could be used. The novel dosing regimen allowed immediate treatment of a patient using a lower dosing rate. This greatly simplifies the current dosing regimen and may reduce NAC adverse effects while ensuring the same amount of NAC is delivered.

  5. ACCELERATED REGIMENS OF ADJUVANT RADIOTHERAPY IN THE TREATMENT OF BREAST CANCER

    Directory of Open Access Journals (Sweden)

    G. V. Afonin

    2017-01-01

    Full Text Available Treatment of breast cancer (BC is a complex multidisciplinary problem. Often, radiation therapy is an obligatory component of treatment of breast cancer patients. Numerous large randomized trials have proved the efficacy of adjuvant radiotherapy in both the standard fractionation regimen in a single focal dose of 2 Gy to a total focal dose of 50 Gy for 25 fractions and in modes of hypofractionation using radiation exposure at a larger daily dose with a reduction in the total treatment time. The presented review summarizes the data of the largest studies on the modes of hypofractionation of postoperative radiotherapy for breast cancer. Most of the studies comparing the standard mode of fractionation of postoperative radiotherapy with the modes of hypofractionation showed comparable results for the main oncological parameters with similar tolerability, frequency of complications and good cosmetic results. It also shows the economic feasibility of applying accelerated regimes in everyday practice. Despite the fact that radiotherapy in the mode of hypofractionation has already become the standard of treatment and is recommended for use by the largest European and American cancer associations, indications for its conduct, the criteria for selection in the studies and the range of recommended single focal doses differ. The obtained results do not give an opportunity to confidently judge the advantage of one or another regime. It is necessary to determine the factors of a favorable and unfavorable prognosis, to clarify the indications for the use of various radiotherapy techniques. Therefore, questions about the optimal mode of hypo-fractionation of adjuvant radiotherapy, the timing of its initiation and the criteria for selecting patients for this type of therapy as part of the comprehensive treatment of breast cancer have not yet been fully resolved. Also open is the choice of optimal single and total doses of radiation, its combination with drug

  6. Virologic failures on initial boosted-PI regimen infrequently possess low-level variants with major PI resistance mutations by ultra-deep sequencing.

    Directory of Open Access Journals (Sweden)

    Max Lataillade

    Full Text Available It is unknown whether HIV-positive patients experiencing virologic failure (VF on boosted-PI (PI/r regimens without drug resistant mutations (DRM by standard genotyping harbor low-level PI resistant variants. CASTLE compared the efficacy of atazanavir/ritonavir (ATV/r with lopinavir/ritonavir (LPV/r, each in combination with TVD in ARV-naïve subjects.To determine if VF on an initial PI/r-based regimen possess low-level resistant variants that may affect a subsequent PI-containing regimen.Patients experiencing VF on a Tenofovir/Emtricitabine+PI/r regimen were evaluated by ultra deep sequencing (UDS for mutations classified/weighted by Stanford HIVdb. Samples were evaluated for variants to 0.4% levels. 36 VF subjects were evaluated by UDS; 24 had UDS for PI and RT DRMs. Of these 24, 19 (79.2% had any DRM by UDS. The most common UDS-detected DRM were NRTI in 18 subjects: M184V/I (11, TAMs(7 & K65R(4; PI DRMs were detected in 9 subjects: M46I/V(5, F53L(2, I50V(1, D30N(1, and N88S(1. The remaining 12 subjects, all with VLs12 for ATV or LPV: N88S (at 0.43% level-mutational load 1,828 in 1 subject on ATV; I50V (0.44%-mutational load 110 and L76V (0.52%-mutational load 20 in 1 subject each, both on LPV. All VF samples remained phenotypically susceptible to the treatment PI/r.Among persons experiencing VF without PI DRMs with standard genotyping on an initial PI/r regimen, low-level variants possessing major PI DRMs were present in a minority of cases, occurred in isolation, and did not result in phenotypic resistance. NRTI DRMs were detected in a high proportion of subjects. These data suggest that PIs may remain effective in subjects experiencing VF on a PI/r-based regimen when PI DRMs are not detected by standard or UDS genotyping.

  7. Variability in Antibiotic Regimens for Surgical Necrotizing Enterocolitis Highlights the Need for New Guidelines.

    Science.gov (United States)

    Blackwood, Brian P; Hunter, Catherine J; Grabowski, Julia

    Necrotizing enterocolitis or NEC is the most common gastrointestinal emergency in the newborn. The etiology of NEC remains unknown, and treatment consists of antibiotic therapy and supportive care with the addition of surgical intervention as necessary. Unlike most surgical diseases, clear guidelines for the type and duration of peri-operative antibiotic therapy have not been established. Our aim was to review the antibiotic regimen(s) applied to surgical patients with NEC within a single neonatal intensive care unit (NICU) and to evaluate outcomes and help develop guidelines for antibiotic administration in this patient population. A single-center retrospective review was performed of all patients who underwent surgical intervention for NEC from August 1, 2005 through August 1, 2015. Relevant data were extracted including gestational age, age at diagnosis, gender, pre-operative antibiotic treatment, post-operative antibiotic treatment, development of stricture, and mortality. Patients were excluded if there was incomplete data documentation. A total of 90 patients were identified who met inclusion criteria. There were 56 male patients and 34 female patients. The average gestational age was 30 5/7 wks and average age of diagnosis 16.7 d. A total of 22 different pre-operative antibiotic regimens were identified with an average duration of 10.6 d. The most common pre-operative regimen was ampicillin, gentamicin, and metronidazole for 14 d. A total of 15 different post-operative antibiotic regimens were identified with an average duration of 6.6 d. The most common post-operative regimen was ampicillin, gentamicin, and metronidazole for two days. There were 26 strictures and 15 deaths. No regimen or duration proved superior. We found that there is a high degree of variability in the antibiotic regimen for the treatment of NEC, even within a single NICU, with no regimen appearing superior over another. As data emerge that demonstrate the adverse effects of

  8. Comparing interval and continuous exercise training regimens on neurotrophic factors in rat brain.

    Science.gov (United States)

    Afzalpour, Mohammad Esmaiel; Chadorneshin, Hossein Taheri; Foadoddini, Mohsen; Eivari, Hossein Abtahi

    2015-08-01

    The research literature suggests that oxidative stress and pro-inflammatory factors influence neurotrophins in vitro. However, there is insufficient information about their effects on exercise training conditions, especially during high intensity trainings. This study aimed to compare the effects of 6weeks of high intensity interval and continuous training regimens on brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), hydrogen peroxide (H2O2), and tumor necrosis factor alpha (TNF-α) in the rat brain. For this purpose, twenty-four Albino Wistar rats were divided into sedentary control (SC), high intensity interval training (HIIT), and continuous training (CT) groups. Both HIIT and CT regimens increased H2O2 level and TNF-α concentration in the brain, and the alterations made were greater following HIIT than CT. In addition, both HIIT and CT regimens increased BDNF and GDNF concentrations significantly, with a higher elevation following HIIT than CT. Furthermore, H2O2 level and TNF-α concentration correlated positively with both BDNF and GDNF concentrations. Generally, high intensity interval training regimen, rather than continuous training regimen, is highly potential to improve BDNF and GDNF through a greater increase in H2O2 and TNF-α as oxidative stress and pro-inflammatory factors. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Cleansing the colon in gallium-67 scintigraphy: a prospective comparison of regimens

    International Nuclear Information System (INIS)

    Novetsky, G.J.; Turner, D.A.; Ali, A.; Raynor, W.J.; Fordham, E.W.

    1981-01-01

    Colonic accumulation of gallium-67 frequently complicates the interpretation of gallium-67 scintigrams. Although various modes of cleansing the colon prior to scintigraphy have been suggested, there is controversy over their efficacy and none have been tested prospectively. Three hundred nine patients undergoing gallium-67 scintigraphy were randomly assigned to one of four cleansing regimens: (1) a high fiber diet (78 patients); (2) castor oil (76); (3) milk of magnesia and cascara (76); and (4) no preparation (79). Patient compliance rates for the four regimens were 17%, 32%, 36%, and 46%, respectively. After noncompliant patients were excluded, gallium-67 scintigrams were graded for colonic activity on a scale of 0-3 by three independent, experienced observers. Gallium-67 activity in the colon was significantly less after adminstration of castor oil than after no prepartion (p = 0.083). Regimen 3 did not produce significantly better results than regimen 4 (p = 0.42). A major impediment to the success of any cleansing regimen seems to be poor compliance of patients

  10. Cleansing the colon in gallium-67 scintigraphy: a prospective comparison of regimens.

    Science.gov (United States)

    Novetsky, G J; Turner, D A; Ali, A; Raynor, W J; Fordham, E W

    1981-11-01

    Colonic accumulation of gallium-67 frequently complicates the interpretation of gallium-67 scintigrams. Although various modes of cleansing the colon prior to scintigraphy have been suggested, there is controversy over their efficacy and none have been tested prospectively. Three hundred nine patients undergoing gallium-67 scintigraphy were randomly assigned to one of four cleansing regimens: (1) a high fiber diet (78 patients); (2) castor oil (76); (3) milk of magnesia and cascara (76); and (4) not preparation (79). Patient compliance rates for the four regimens were 17%, 32%, 36%, and 46%, respectively. After noncompliant patients were excluded, gallium-67 scintigrams were graded for colonic activity on a scale of 0-3 by three independent, experienced observers. Gallium-67 activity in the colon was significantly less after administration of castor oil than after no preparation (p = 0.047). A high fiber diet also resulted in a substantial reduction of colonic activity when compared with no preparation; the difference, however, was not statistically significant (p = 0.083). Regimen 3 did not produce significantly better results than regimen 4 (p = 0.42). A major impediment to the success of any cleansing regimen seems to be poor compliance of patients.

  11. Cleansing the colon in gallium-67 scintigraphy: a prospective comparison of regimens

    International Nuclear Information System (INIS)

    Novetsky, G.J.; Turner, D.A.; Ali, A.; Raynor, W.J. Jr.; Fordham, E.W.

    1981-01-01

    Colonic accumulation of gallium-67 frequently complicates the interpretation of gallium-67 scintigrams. Although various modes of cleansing the colon prior to scintigraphy have been suggested, there is controversy over their efficacy and none have been tested prospectively. Three hundred nine patients undergoing gallium-67 scintigraphy were randomly assigned to one of four cleansing regimens: (1) a high fiber diet (78 patients); (2) castor oil (76); (3) milk of magnesia and cascara (76); and (4) not preparation (79). Patient compliance rates for the four regimens were 17%, 32%, 36%, and 46%, respectively. After noncompliant patients were excluded, gallium-67 scintigrams were graded for colonic activity on a scale of 0-3 by three independent, experienced observers. Gallium-67 activity in the colon was significantly less after administration of castor oil than after no preparation (p . 0.047). A high fiber diet also resulted in a substantial reduction of colonic activity when compared with no preparation; the difference, however, was not statistically significant (p . 0.083). Regimen 3 did not produce significantly better results than regimen 4 (p . 0.42). A major impediment to the success of any cleansing regimen seems to be poor compliance of patients

  12. Dealing with large-scale supply lines when introducing new regimens.

    Science.gov (United States)

    Malati, Christine; Rosenfeld, Joshua; Mowafy, Sherif; Rittmiller, Trevor; Kuritsky, Joel; Crowley, John

    2017-07-01

    As programs plan the introduction of a new antiretroviral as part of a regimen for HIV treatment, supply chain considerations need to be taken into account. The key to success is balancing the introduction of a new regimen with the phasing out of an old regimen in a manner that does not result in either a shortage or an excess supply of either product while ensuring that patients continue receiving their medications. This necessitates that country programs, donors, and procurement entities possess an appreciation of the global antiretroviral market and understand the dynamics that the manufacturing of new antiretrovirals will have on the transition. Supply, demand, and financial considerations affect the capacity of the supply chain to facilitate a successful antiretroviral transition. Although this commentary draws on United States Agency for International Development experiences under the President's Emergency Plan for AIDS Relief from earlier antiretroviral treatment shifts, the approaches are applicable to other institutions and to future transitions. Three approaches were employed: ensuring the engagement of all key stakeholders in transition planning and execution, including clinicians, advocacy groups, supply chain professionals, ministry, and donors; conducting and updating regularly the national quantification and supply plans for all regimens; and introducing antiretroviral products into programs from regional warehouses based on firm orders. Extensive planning and accounting for supply chain factors is essential to ensuring a smooth transition to a new regimen and to enable the global antiretroviral market to respond adequately.

  13. Comparative study of short term results in two multidrug regimens in multibacillary leprosy.

    Science.gov (United States)

    Singh, R P; Tiwari, V D; Chattopadhyay, S P

    1993-01-01

    Thirty lepromatous and Borderline lepromatous leprosy patients were treated with multidrug therapy in an open trial. Fifteen of them received the standard WHO multidrug regimen ie., rifampicin 600 mg and clofazimine 300 mg monthly, supervised, and dapsone 100 mg daily and clofazimine 100 mg on alternate days as self administered; the other 15 received a modified multidrug therapy regimen comprising of rifampicin 600 mg, clofazimine 100 mg and dapsone 100 mg daily for 21 days as suggested by the Indian Association of Leprologists, followed by the standard WHO regimen. The observation period was six months. Clinical, bacteriological, histological and immunological parameters were studied. The fall in morphological index was much faster in patients receiving modified multidrug therapy regimen compared to those receiving the standard WHO regimen. Otherwise, there was no difference between the two groups of patients. Five patients developed type I (upgrading) reaction with one developing ulnar nerve paralysis. No untoward effects of drugs were noted in the study subjects except for darkening of skin colour of all the patients.

  14. Assessment of serum magnesium levels and its outcome in neonates of eclamptic mothers treated with low-dose magnesium sulfate regimen

    Science.gov (United States)

    Das, Monalisa; Chaudhuri, Patralekha Ray; Mondal, Badal C.; Mitra, Sukumar; Bandyopadhyay, Debasmita; Pramanik, Sushobhan

    2015-01-01

    Objectives: Magnesium historically has been used for treatment and/or prevention of eclampsia. Considering the low body mass index of Indian women, a low-dose magnesium sulfate regime has been introduced by some authors. Increased blood levels of magnesium in neonates is associated with increased still birth, early neonatal death, birth asphyxia, bradycardia, hypotonia, gastrointestinal hypomotility. The objective of this study was to assess safety of low-dose magnesium sulfate regimen in neonates of eclamptic mothers treated with this regimen. Materials and Methods: This was a cross-sectional observational study of 100 eclampsia patients and their neonates. Loading dose and maintenance doses of magnesium sulfate were administered to patients by combination of intravenous and intramuscular routes. Maternal serum and cord blood magnesium levels were estimated. Neonatal outcome was assessed. Results: Bradycardia was observed in 18 (19.15%) of the neonates, 16 (17.02%) of the neonates were diagnosed with hypotonia. Pearson Correlation Coefficient showed Apgar scores decreased with increase in cord blood magnesium levels. Unpaired t-test showed lower Apgar scores with increasing dose of magnesium sulfate. The Chi-square/Fisher's exact test showed significant increase in hypotonia, birth asphyxia, intubation in delivery room, Neonatal Intensive Care Unit (NICU) care requirement, with increasing dose of magnesium sulfate. (P ≤ 0.05). Conclusion: Several neonatal complications are significantly related to increasing serum magnesium levels. Overall, the low-dose magnesium sulfate regimen was safe in the management of eclamptic mothers, without toxicity to their neonates. PMID:26600638

  15. Choice of first-line antiretroviral therapy regimen and treatment outcomes for HIV in a middle income compared to a high income country: a cohort study.

    Science.gov (United States)

    Dragovic, Gordana; Smith, Colette J; Jevtovic, Djordje; Dimitrijevic, Bozana; Kusic, Jovana; Youle, Mike; Johnson, Margaret A

    2016-03-03

    The range of combination antiretroviral therapy (cART) regimens available in many middle-income countries differs from those suggested in international HIV treatment guidelines. We compared first-line cART regimens, timing of initiation and treatment outcomes in a middle income setting (HIV Centre, Belgrade, Serbia - HCB) with a high-income country (Royal Free London Hospital, UK - RFH). All antiretroviral-naïve HIV-positive individuals from HCB and RFH starting cART between 2003 and 2012 were included. 12-month viral load and CD4 count responses were compared, considering the first available measurement 12-24 months post-cART. The percentage that had made an antiretroviral switch for any reason, or for toxicity and the percentage that had died by 36 months (the latest time at which sufficient numbers remained under follow-up) were investigated using standard survival methods. 361/597 (61 %) of individuals initiating cART at HCB had a prior AIDS diagnosis, compared to 337/1763 (19 %) at RFH. Median pre-ART CD4 counts were 177 and 238 cells/mm(3) respectively (p HIV disease, resulting in higher mortality rates than in high income countries, supporting improved testing campaigns for early detection of HIV infection and early introduction of newer cART regimens.

  16. Revisiting dosing regimen using PK/PD modeling: the MODEL1 phase I/II trial of docetaxel plus epirubicin in metastatic breast cancer patients.

    Science.gov (United States)

    Hénin, Emilie; Meille, Christophe; Barbolosi, Dominique; You, Benoit; Guitton, Jérôme; Iliadis, Athanassios; Freyer, Gilles

    2016-04-01

    The MODEL1 trial is the first model-driven phase I/II dose-escalation study of densified docetaxel plus epirubicin administration in metastatic breast cancer patients, a regimen previously known to induce unacceptable life-threatening toxicities. The primary objective was to determine the maximum tolerated dose of this densified regimen. Study of the efficacy was a secondary objective. Her2-negative, hormone-resistant metastatic breast cancer patients were treated with escalating doses of docetaxel plus epirubicin every 2 weeks for six cycles with granulocyte colony stimulating factor support. A total of 16 patients were treated with total doses ranging from 85 to 110 mg of docetaxel plus epirubicin per cycle. Dose escalation was controlled by a non-hematological toxicity model. Dose densification was guided by a model of neutrophil kinetics, able to optimize docetaxel plus epirubicin dosing with respect to pre-defined acceptable levels of hematological toxicity while ensuring maximal efficacy. The densified treatment was safe since hematological toxicity was much lower compared to previous findings, and other adverse events were consistent with those observed with this regimen. The maximal tolerated dose was 100 mg given every 2 weeks. The response rate was 45 %; median progression-free survival was 10.4 months, whereas 54.6 months of median overall survival was achieved. The optimized docetaxel plus epirubicin dosing regimen led to fewer toxicities associated with higher efficacy as compared with standard or empirical densified dosing. This study suggests that model-driven dosage adjustment can lead to improved efficacy-toxicity balance in patients with cancer when several anticancer drugs are combined.

  17. Cancer Chemotherapy Update: Bevacizumab, Etoposide, and Cisplatin Regimen for Refractory Brain Metastases.

    Science.gov (United States)

    Mayer, Seth A; Solimando, Dominic A; Waddell, J Aubrey

    2017-06-01

    The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc, 4201 Wilson Blvd #110-545, Arlington, VA 22203, email: OncRxSvc@comcast.net; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, email: waddfour@charter.net. Regimen Name: Bevacizumab, etoposide, and cisplatin (BEEP) Origin of Name: The regimen is named for the medications it contains: be vacizumab, e toposide, and cis p latin.

  18. Peri-operative glycaemic control regimens for preventing surgical site infections in adults.

    Science.gov (United States)

    Kao, Lillian S; Meeks, Derek; Moyer, Virginia A; Lally, Kevin P

    2009-07-08

    Surgical site infections (SSIs) are associated with significant morbidity, mortality, and resource utilization and are potentially preventable. Peri-operative hyperglycaemia has been associated with increased SSIs and previous recommendations have been to treat glucose levels above 200 mg/dL. However, recent studies have questioned the optimal glycaemic control regimen to prevent SSIs. Whether the benefits of strict or intensive glycaemic control with insulin infusion as compared to conventional management outweigh the risks remains controversial. To summarise the evidence for the impact of glycaemic control in the peri-operative period on the incidence of surgical site infections, hypoglycaemia, level of glycaemic control, all-cause and infection-related mortality, and hospital length of stay and to investigate for differences of effect between different levels of glycaemic control. A search strategy was developed to search the following databases: Cochrane Wounds Group Specialised Register (searched 25 March 2009), The Cochrane Central Register of Controlled Trials, The Cochrane Library 2009, Issue 1; Ovid MEDLINE (1950 to March Week 2 2009); Ovid EMBASE (1980 to 2009 Week 12) and EBSCO CINAHL (1982 to March Week 3 2009). The search was not limited by language or publication status. Randomised controlled trials (RCTs) were eligible for inclusion if they evaluated two (or more) glycaemic control regimens in the peri-operative period (within one week pre-, intra-, and/or post-operative) and reported surgical site infections as an outcome. The standard method for conducting a systematic review in accordance with the Cochrane Wounds Group was used. Two review authors independently reviewed the results from the database searches and identified relevant studies. Two review authors extracted study data and outcomes from each study and reviewed each study for methodological quality. Any disagreement was resolved by discussion or by referral to a third review author. Five

  19. A randomized trial evaluating a block-replacement regimen during radioiodine therapy

    DEFF Research Database (Denmark)

    Bonnema, Steen J; Grupe, Peter; Boel-Jørgensen, Henrik

    2011-01-01

    Eur J Clin Invest 2010 ABSTRACT: Background  Lack of consensus regarding the antithyroid drug regimen in relation to radioiodine ((131) I) therapy of hyperthyroidism prompted this randomized trial comparing two strategies. Design  Patients with Graves' disease (GD, n = 51) or toxic nodular goitre...... (TNG, n = 49) were randomized to (131) I either 8 days following discontinuation of methimazole (-BRT, n = 52, median dose: 5 mg) or while on a continuous block-replacement regimen (+BRT, n = 48, median dose 15 mg methimazole and 100 μg levothyroxine). Results  Patients in the +BRT group required more...

  20. Esomeprazole regimens for reflux symptoms in Chinese patients with chronic gastritis.

    Science.gov (United States)

    Sun, Jing; Yuan, Yao-Zong; Hou, Xiao-Hua; Zou, Duo-Wu; Lu, Bin; Chen, Min-Hu; Liu, Fei; Wu, Kai-Chun; Zou, Xiao-Ping; Li, Yan-Qing; Zhou, Li-Ya

    2015-06-14

    To compare symptom control with esomeprazole regimens for non-erosive reflux disease and chronic gastritis in patients with a negative endoscopy. This randomized, open-label study was designed in line with clinical practice in China. Patients with typical reflux symptoms for ≥ 3 mo and a negative endoscopy who had a Gastroesophageal Reflux Disease Questionnaire score ≥ 8 were randomized to initial treatment with esomeprazole 20 mg once daily either for 8 wk or for 2 wk. Patients with symptom relief could enter another 24 wk of maintenance/on-demand treatment, where further courses of esomeprazole 20 mg once daily were given if symptoms recurred. The primary endpoint was the symptom control rate at week 24 of the maintenance/on-demand treatment period. Secondary endpoints were symptom relief rate, success rate (defined as patients who had symptom relief after initial treatment and after 24 wk of maintenance treatment), time-to-first-relapse and satisfaction rate. Based on the data collected in the modified intention-to-treat population (MITT; patients in the ITT population with symptom relief after initial esomeprazole treatment, n = 262), the symptom control rate showed a small but statistically significant difference in favor of the 8-wk regimen (94.9% vs 87.3%, P = 0.0473). Among the secondary endpoints, based on the data collected in the ITT population (n = 305), the 8-wk group presented marginally better results in symptom relief after initial esomeprazole treatment (88.3% vs 83.4%, P = 0.2513) and success rate over the whole study (83.8% vs 72.8%, P = 0.0258). The 8-wk regimen was found to provide a 46% reduction in risk of relapse vs the 2-wk regimen (HR = 0.543; 95%CI: 0.388-0.761). In addition, fewer unscheduled visits and higher patient satisfaction supported the therapeutic benefits of the 8-wk regimen over the 2-wk regimen. Safety was comparable between the two groups, with both regimens being well tolerated. Chinese patients diagnosed with chronic

  1. Recent developments in the treatment of obesity with particular reference to semistarvation ketogenic regimens.

    Science.gov (United States)

    Bistrian, B R

    1978-01-01

    Three new techniques have been developed for the treatment of obesity--behavior modification, semistarvation ketogenic regimens, and surgical therapy. Behavior modification appears to be effective for weight maintenance after weight loss through balanced deficit dieting for patients at less than 130 per cent of desirable body weight and semistarvation ketogenic regimens for patients from 130 to 200 per cent of desirable body weight. When indicated, surgical therapy is more efficacious for patients who are in excess of 200 per cent desirable body weight. All three approaches should be considered experimental until a larger experience is acquired and preliminary results are confirmed.

  2. Individualized Ranibizumab Regimen Driven by Stabilization Criteria for Central Retinal Vein Occlusion

    DEFF Research Database (Denmark)

    Larsen, Michael; Waldstein, Sebastian M; Boscia, Francesco

    2016-01-01

    PURPOSE: To assess the 12-month efficacy and safety profile of an individualized regimen of ranibizumab 0.5 mg driven by stabilization criteria in patients with macular edema secondary to central retinal vein occlusion (CRVO). DESIGN: A 24-month, prospective, open-label, single-arm, multicenter...... with higher baseline BCVA. No new ocular or nonocular safety events were observed. CONCLUSIONS: An individualized dosing regimen of ranibizumab 0.5 mg driven by stabilization criteria for up to 12 months resulted in significant BCVA gain in a broad population of patients with macular edema secondary to CRVO...

  3. Neoadjuvant Therapy of DOF Regimen Plus Bevacizumab Can Increase Surgical Resection Ratein Locally Advanced Gastric Cancer: A Randomized, Controlled Study.

    Science.gov (United States)

    Ma, Junxun; Yao, Sheng; Li, Xiao-Song; Kang, Huan-Rong; Yao, Fang-Fang; Du, Nan

    2015-10-01

    Locally advanced gastric cancer (LAGC) is best treated with surgical resection. Bevacizumab in combination with chemotherapy has shown promising results in treating advanced gastric cancer. This study aimed to investigate the efficacy of neoadjuvant chemotherapy using the docetaxel/oxaliplatin/5-FU (DOF) regimen and bevacizumab in LAGC patients.Eighty LAGC patients were randomized to receive DOF alone (n = 40) or DOF plus bevacizumab (n = 40) as neoadjuvant therapy before surgery. The lesions were evaluated at baseline and during treatment. Circulating tumor cells (CTCs) were counted using the FISH test. Patients were followed up for 3 years to analyze the disease-free survival (DFS) and overall survival (OS).The total response rate was significantly higher in the DOF plus bevacizumab group than the DOF group (65% vs 42.5%, P = 0.0436). The addition of bevacizumab significantly increased the surgical resection rate and the R0 resection rate (P DOF plus bevacizumab group showed significantly greater reduction in CTC counts after neoadjuvant therapy in comparison with the DOF group (P = 0.0335). Although the DOF plus bevacizumab group had significantly improved DFS than the DOF group (15.2 months vs 12.3 months, P = 0.013), the 2 groups did not differ significantly in OS (17.6 ± 1.8 months vs 16.4 ± 1.9 months, P = 0.776. Cox proportional model analysis showed that number of metastatic lymph nodes, CTC reduction, R0 resection, and neoadjuvant therapy are independent prognostic factors for patients with LAGC.Neoadjuvant of DOF regimen plus bevacizumab can improve the R0 resection rate and DFS in LAGC. These beneficial effects might be associated with the reduction in CTC counts.

  4. Use of metronidazole as part of an empirical antibiotic regimen after incision and drainage of infections of the odontogenic spaces.

    Science.gov (United States)

    Bali, Rishi; Sharma, Parveen; Gaba, Shivani

    2015-01-01

    The combination of amoxicillin/clavulanate and metronidazole is a widely-accepted empirical regimen for infections of the odontogenic spaces. Once adequate drainage has been established micro-organisms are less likely to grow and multiply, particularly anaerobes. This may obviate the need for anaerobic coverage after drainage in healthy hosts. We studied 60 patients in this randomised prospective study, the objective of which was to evaluate metronidazole as part of an empirical antibiotic regimen after drainage of infections of the odontogenic spaces. Samples of pus were sent for culture and testing for sensitivity. Amoxicillin/clavulanate and metronidazole were given to all patients. After incision and drainage the patients were randomly allocated to two groups. In the first group both antibiotics were continued, and in the second metronidazole was withdrawn. The groups were compared both clinically and microbiologically. There were no significant differences between the groups in the resolution of infection. Thirteen patients (n=6 in the 2-antimicrobial group, and n=7 in the amoxicillin/clavulanate group) showed no improvement during the 48 h postoperatively. Overall there was need to substitute another antibiotic for amoxicillin/clavulanate in only 6 cases. Six patients in the amoxicillin/clavulanate group required the addition of metronidazole after drainage. We conclude that in healthy subjects metronidazole is not necessary in the period after drainage, but its prescription should be based on assessment of clinical and laboratory markers of infection. Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  5. A randomized trial to evaluate continuation versus discontinuation fo lamivudine in individuals failing a lamivudine-containing regimen: the COLATE trial

    DEFF Research Database (Denmark)

    Fox, Zoe; Dragsted, Ulrik Bak; Gerstoft, J

    2006-01-01

    BACKGROUND: Lamivudine (3TC) therapy can cause the emergence of M1841/V. Previous studies suggest a higher fidelity of the mutant reverse transcriptase and lower replication capacity of the mutant virus. No data exist from clinical comparative studies evaluating the benefit of M1841/V in patients...... receiving combination antiretroviral therapy (cART). METHODS: HIV-1-infected adults failing a 3TC-containing regimen were randomized to continue (On-3TC) or discontinue 3TC (Off-3TC) whilst receiving cART. The primary efficacy measure was the log10 average-area-under-the-curve-minus-baseline reduction...

  6. Selection of non-steroidal anti-inflammatory drug and treatment regimen for sulfur mustard-induced cutaneous lesions.

    Science.gov (United States)

    Plahovinsak, Jennifer L; Buccellato, Matthew A; Reid, Frances M; Graham, John S

    2016-09-01

    The inflammatory process plays an important role in sulfur mustard (HD) injury and HD pathogenesis, suggesting that anti-inflammatory treatments applied as soon as possible following HD injury may reduce tissue damage and accelerate healing. This study used the HD dermal weanling swine model to investigate the efficacy of two non-steroidal anti-inflammatory drugs, capsaicin and diclofenac, when applied in combination with the steroid, clobetasol. The therapeutic regimen was also investigated with respect to initiation of treatment post-exposure, frequency and duration. Yorkshire-cross pigs were randomly assigned to experimental groups, corresponding to all combinations of treatment (capsaicin with clobetasol or diclofenac with clobetasol), onset time (1, 2 or 4 h post-exposure), treatment duration (1, 3 or 5 days) and frequency of applications (2, 3 or 4 per day). For each animal, two sites on the ventral abdomen were exposed to 400 μL of neat HD for 8 min to achieve superficial dermal (SD) lesions and two sites were exposed to 400 μL neat HD for 30 min to achieve deep dermal (DD) lesions. Each treatment regimen was tested against a SD and a DD injury. Untreated SD and DD lesion sites served as within-animal controls. Assessments, up to one week post-challenge, included digital photographs, clinical assessments (lesion size measurements and modified Draize scoring), transepidermal water loss (TEWL), reflectance colorimetry and histopathologic evaluations that included an estimate for depth of injury and wound healing parameters. Diclofenac plus clobetasol treatment resulted in significant reductions in lesion contracture and modified Draize scores, increased barrier function (decreased TEWL), and increased healing as determined by histopathology for both SD and DD injury when compared with untreated sites and sites treated with capsaicin plus clobetasol. An increased duration of treatment from 1 to 5 days was most commonly associated with decreased

  7. Winning Combinations

    DEFF Research Database (Denmark)

    Criscuolo, Paola; Laursen, Keld; Reichstein, Toke

    2018-01-01

    Searching for the most rewarding sources of innovative ideas remains a key challenge in management of technological innovation. Yet, little is known about which combinations of internal and external knowledge sources are triggers for innovation. Extending theories about searching for innovation, we...... examine the effectiveness of different combinations of knowledge sources for achieving innovative performance. We suggest that combinations involving integrative search strategies – combining internal and external knowledge – are the most likely to generate product and process innovation. In this context...

  8. PROPOSAL OF ANTI-TUBERCULOSIS REGIMENS BASED ON SUSCEPTIBILITY TO ISONIAZID AND RIFAMPICIN

    Science.gov (United States)

    Mendoza-Ticona, Alberto; Moore, David AJ; Alarcón, Valentina; Samalvides, Frine; Seas, Carlos

    2014-01-01

    Objective To elaborate optimal anti-tuberculosis regimens following drug susceptibility testing (DST) to isoniazid (H) and rifampicin (R). Design 12 311 M. tuberculosis strains (National Health Institute of Peru 2007-2009) were classified in four groups according H and R resistance. In each group the sensitivity to ethambutol (E), pirazinamide (Z), streptomycin (S), kanamycin (Km), capreomycin (Cm), ciprofloxacin (Cfx), ethionamide (Eto), cicloserine (Cs) and p-amino salicilic acid (PAS) was determined. Based on resistance profiles, domestic costs, and following WHO guidelines, we elaborated and selected optimal putative regimens for each group. The potential efficacy (PE) variable was defined as the proportion of strains sensitive to at least three or four drugs for each regimen evaluated. Results Selected regimes with the lowest cost, and highest PE of containing 3 and 4 effective drugs for TB sensitive to H and R were: HRZ (99,5%) and HREZ (99,1%), respectively; RZECfx (PE=98,9%) and RZECfxKm (PE=97,7%) for TB resistant to H; HZECfx (96,8%) and HZECfxKm (95,4%) for TB resistant to R; and EZCfxKmEtoCs (82.9%) for MDR-TB. Conclusion Based on resistance to H and R it was possible to select anti-tuberculosis regimens with high probability of success. This proposal is a feasible alternative to tackle tuberculosis in Peru where the access to rapid DST to H and R is improving progressively. PMID:23949502

  9. Effectiveness of a triple-drug regimen for global elimination of lymphatic filariasis: A modelling study

    NARCIS (Netherlands)

    M.A. Irvine (Michael A.); W.A. Stolk (Wilma); Smith, M.E. (Morgan E); S.V. Subramanian; B.K. Singh (Brajendra K.); G.J. Weil (Gary); E. Michael (Edwin); T.D. Hollingsworth (T. Déirdre)

    2017-01-01

    textabstractBackground: Lymphatic filariasis is targeted for elimination as a public health problem by 2020. The principal approach used by current programmes is annual mass drug administration with two pairs of drugs with a good safety profile. However, one dose of a triple-drug regimen

  10. Expert opinion on a flexible extended regimen of drospirenone/ethinyl estradiol contraceptive.

    Science.gov (United States)

    Han, Leo; Jensen, Jeffrey T

    2014-10-01

    Oral contraceptives are often prescribed in extended or continuous forms in order to manage menstrual bleeding and menstrual-related side effects. However, with extended regimens, unscheduled intracycle bleeding can become problematic. Flexible extended dosing of a contraceptive containing drospirenone (DRSP) and ethinyl estradiol (EE) was designed to improve bleeding profiles during extended cycles through active management of bleeding symptoms. We examine the rationale for flexible extended dosing as well as review the dosing regimen. We will focus on the findings of the two most important clinical trials regarding flexible extended DRSP/EE (3 mg/20 μg), including the bleeding profiles of women in those trials. Pharmacology, mechanisms of action, efficacy as well as safety of DRSP containing pills will also be reviewed. Flexible extended dosing of DRSP/EE (3 mg/20 μg) has similar pharmacokinetics and contraceptive efficacy of both conventional and fixed extended regimens. However, it has the added benefit of fewer days of bleeding/spotting compared to conventional and fixed extended regimens.

  11. Efficacy of homecare regimens for mechanical plaque removal in managing gingivitis: a meta review

    NARCIS (Netherlands)

    van der Weijden, F.A.; Slot, D.E.

    2015-01-01

    Focused question Based on evidence as presented in systematic reviews what is the efficacy and safety of available homecare toothbrush regimens for mechanical plaque removal on plaque and gingivitis in adults? Material & Methods Three Internet sources were used (up to and including August 2014) to

  12. Pharmacist consultations: simplifying daily drug regimens and providing education on fall risk for older adults.

    Science.gov (United States)

    Bartlett, Donna; Pang, Nina; Massey, Colleen; Evans, Paula

    2015-03-01

    To evaluate whether a medication review by a pharmacist in the community can simplify an older adult's daily drug regimen and improve awareness of medication-related fall risk. Pre- and posttest with follow-up design. Senior centers, senior housing facilities, and community centers in Massachusetts. Older adults who attended a pharmacy outreach program at a community center. Participants engaged in a one-time, face-to-face, medication therapy management (MTM) session. The pharmacists made recommendations to simplify daily drug regimens for best therapeutic results. The participants were educated regarding the influence that medications may have on fall risk. For the 75 participants, daily dose regimens were significantly reduced. From the presurvey to the follow-up surveys, there was a significant increase of participants taking medication three times or fewer per day (73% to 85%) versus those participants taking medications more than three times per day (P = 0.041). Through MTM consultations, participants' awareness that medications may be a contributing factor to fall risk was increased from 28% in the presurvey to 56% in the postsurvey (P = 0.0018). A pharmacist consultation can simplify the daily drug regimen. Furthermore, consultant pharmacists can educate patients regarding the risk that medications may have on falls.

  13. Calcipotriol cream in the morning and ointment in the evening: a novel regimen to improve compliance.

    NARCIS (Netherlands)

    Kerkhof, P.C.M. van de; Franssen, M.; Brassinne, M. de la; Kuipers, M.V.

    2001-01-01

    BACKGROUND: Calcipotriol ointment and calcipotriol cream have both been shown to be effective in the treatment of psoriasis. AIM: To find out the patient compliance, efficacy and tolerance to a regimen of a calcipotriol cream application in the morning and a calcipotriol ointment application in the

  14. Metabolic drug interactions - the impact of prescribed drug regimens on the medication safety.

    NARCIS (Netherlands)

    Fialova, D.; Vrbensky, K.; Topinkova, E.; Vlcek, J.; Soerbye, L.W.; Wagner, C.; Bernabei, R.

    2005-01-01

    Background and objective: Risk/benefit profile of prescribed drug regimens is unkown. Over 60% of commonly used medications interact on metabolic pathways (cytochrom P450 (CYP450), uridyl-glucuronyl tranferasis (UGT I, II) and P-glycoprotein (PGP) transport). Using an up-to-date knowledge on

  15. Comparative Study on the Efficacy of Two Regimens of Single-Shot ...

    African Journals Online (AJOL)

    ... mother by increasing self esteem and improving bonding with the baby. Objective: To assess and compare the satisfaction and efficacy of two regimens of single-shot spinal blocks for the relief of labor pain in women who present in active phase of labour. Design: A prospective randomised single-blind observational study

  16. The parenteral nutritional regimen in pigs for basic studies in physiology of nutrition

    International Nuclear Information System (INIS)

    Matkowitz, R.; Harting, W.; Souffrant, W.B.; Junghans, P.; Boerner, P.

    1983-01-01

    Experimental studies concerning a parenteral nutritional regimen were performed in pigs aiming at comparative metabolic investigations to evaluate clinically relevant problems within nutritional research. By means of the 15 N tracer technique the evaluation of the postoperative protein turnover was rendered possible by this animal model

  17. Alignment of new tuberculosis drug regimens and drug susceptibility testing: a framework for action

    NARCIS (Netherlands)

    Wells, William A.; Boehme, Catharina C.; Cobelens, Frank G. J.; Daniels, Colleen; Dowdy, David; Gardiner, Elizabeth; Gheuens, Jan; Kim, Peter; Kimerling, Michael E.; Kreiswirth, Barry; Lienhardt, Christian; Mdluli, Khisi; Pai, Madhukar; Perkins, Mark D.; Peter, Trevor; Zignol, Matteo; Zumla, Alimuddin; Schito, Marco

    2013-01-01

    New tuberculosis drug regimens are creating new priorities for drug susceptibility testing (DST) and surveillance. To minimise turnaround time, rapid DST will need to be prioritised, but developers of these assays will need better data about the molecular mechanisms of resistance. Efforts are

  18. Ghost probiotics with a combined regimen: a novel therapeutic approach against the Zika virus, an emerging world threat.

    Science.gov (United States)

    Bajpai, Vivek K; Chandra, Vishal; Kim, Na-Hyung; Rai, Rajni; Kumar, Pradeep; Kim, Kangmin; Aeron, Abhinav; Kang, Sun Chul; Maheshwari, D K; Na, MinKyun; Rather, Irfan A; Park, Yong-Ha

    2018-05-01

    The Zika virus (ZIKV) used to be an obscure flavivirus closely related to dengue virus (DENV). Transmission of this epidemic pathogen occurs mainly via mosquitoes, but it is also capable of placental and sexual transmission. Although the characteristics of these viruses are well defined, infections are unpredictable in terms of disease severity, unusual clinical manifestations, unexpected methods of transmission, long-term persistence, and the development of new strains. Recently, ZIKV has gained huge medical attention following the large-scale epidemics around the world, and reported cases of congenital abnormalities associated with Zika virus infections which have created a public health emergency of international concern. Despite continuous research on ZIKV, no specific treatment or vaccine has been developed, excepting a preventive strategy for congenital ZIKV infection. Probiotics, known as GRAS, are bacteria that confer various health beneficial effects, and have been shown to be effective at curing a number of viral diseases by modulating the immune system. Furthermore, probiotic preparations consisting of dead cells and cellular metabolites, so-called "Ghost probiotics", can also act as biological response modifiers. Here, we review available information on the epidemiology, transmission, and clinical features of ZIKV, and on treatment and prevention strategies. In addition, we emphasize the use of probiotics and plant-based natural remedies and describe their action mechanisms, and the green technologies for microbial conversion, which could contribute to the development of novel therapies that may reduce the pathogenicity of ZIKV. Accordingly, we draw attention to new findings, unanswered questions, unresolved issues, and controversies regarding ZIKV.

  19. Trimegestone in a low-dose, continuous-combined hormone therapy regimen prevents bone loss in osteopenic postmenopausal women

    DEFF Research Database (Denmark)

    Warming, Lise; Ravn, Pernille; Spielman, Danièle

    2004-01-01

    OBJECTIVE: To determine the efficacy of estrogen + progestogen therapy with 1 mg 17beta-estradiol and 0.125 mg trimegestone in the prevention of postmenopausal osteoporosis. DESIGN: For this study, 360 healthy, postmenopausal women with osteopenia [lumbar spine bone mineral density (BMD) between -1...

  20. A tritherapy combination of inactivated allogeneic leukocytes infusion and cell vaccine with cyclophosphamide in a sequential regimen enhances antitumor immunity

    OpenAIRE

    Yishu Tang; Wenbo Ma; Chunxia Zhou; Dongmei Wang; Shuren Zhang

    2018-01-01

    Background: Tumor-induced immunosuppression can impede tumor-specific immune responses and limit the effects of cancer immunotherapy. The aim of this study was to investigate the possible effects of sequential chemoimmunotherapeutic strategies to enhance antitumor immune responses. Methods: Using the E7-expressing tumor TC-1 as the tumor model, the treatment groups were divided into the following groups: (1) inactivated allogeneic leukocyte infusion (ALI), (2) ALI + MMC-inactivated TC-1 cell ...

  1. HCV kinetic and modeling analyses indicate similar time to cure among sofosbuvir combination regimens with daclatasvir, simeprevir or ledipasvir.

    Science.gov (United States)

    Dahari, Harel; Canini, Laetitia; Graw, Frederik; Uprichard, Susan L; Araújo, Evaldo S A; Penaranda, Guillaume; Coquet, Emilie; Chiche, Laurent; Riso, Aurelie; Renou, Christophe; Bourliere, Marc; Cotler, Scott J; Halfon, Philippe

    2016-06-01

    Recent clinical trials of direct-acting-antiviral agents (DAAs) against hepatitis C virus (HCV) achieved >90% sustained virological response (SVR) rates, suggesting that cure often took place before the end of treatment (EOT). We sought to evaluate retrospectively whether early response kinetics can provide the basis to individualize therapy to achieve optimal results while reducing duration and cost. 58 chronic HCV patients were treated with 12-week sofosbuvir+simeprevir (n=19), sofosbuvir+daclatasvir (n=19), or sofosbuvir+ledipasvir in three French referral centers. HCV was measured at baseline, day 2, every other week, EOT and 12weeks post EOT. Mathematical modeling was used to predict the time to cure, i.e., <1 virus copy in the entire extracellular body fluid. All but one patient who relapsed achieved SVR. Mean age was 60±11years, 53% were male, 86% HCV genotype-1, 9% HIV coinfected, 43% advanced fibrosis (F3), and 57% had cirrhosis. At weeks 2, 4 and 6, 48%, 88% and 100% of patients had HCV<15IU/ml, with 27%, 74% and 91% of observations having target not detected, respectively. Modeling results predicted that 23 (43%), 16 (30%), 7 (13%), 5 (9%) and 3 (5%) subjects were predicted to reach cure within 6, 8, 10, 12 and 13weeks of therapy, respectively. The modeling suggested that the patient who relapsed would have benefitted from an additional week of sofosbuvir+ledipasvir. Adjusting duration of treatment according to the modeling predicts reduced medication costs of 43-45% and 17-30% in subjects who had HCV<15IU/ml at weeks 2 and 4, respectively. The use of early viral kinetic analysis has the potential to individualize duration of DAA therapy with a projected average cost saving of 16-20% per 100-treated persons. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  2. Systemic Chemotherapy using FLOT - Regimen Combined with Cytoreductive Surgery plus HIPEC for Treatment of Peritoneal Metastasized Gastric Cancer. .

    Science.gov (United States)

    Müller, H; Hotopp, Th; Tofeili, A; Wutke, K

    2014-05-01

    The aim was to evaluate the feasibility and the effectiveness of neoadjuvant systemic chemotherapy using FLOT - protocol followed by cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC) followed by systemic chemotherapyand in patients with peritoneal carciriomatosis (PC) from gastric cancer. Twenty six (median age 53 years, range 39 - 71) were scheduled for three cycles of neoadjuvant systemic chemotherapy using bi-weekly FLOT - protocol followed by CRS + HIPEC. Thereafter 3 additional cycles of FLOT were given. During HIPEC in Colliseum technique Oxaliplatin was given in a dosage of 200 mg/m2 and Docetaxel in a dosage of 80 mg/m2. All patients underwent cytoreductive surgery plus HIPEC. Peritoneal Cancer index was > 15 in 3 cases only. Complete resection could be carried out in all cases (CC-O 18, CC-18). Postoperative complication rate was 23% with no mortality within 30 days. Anastomotic leakage rate was 3.2%. Overall survival was 19.0 months with a 2-year survival rate 38%. Regression analysis demonstrated a Peritoneal Cancer Index PCI > 12 as negative factor for survival. Neoadju- vant chemotherapy using FLOT - protocol followed by CRS + HIPEC seems to be associated with prolonged OS in patients with peritoneal carcinomatosis from gastric cancer. This treatment is not recommended for patients with extensive peritoneal involvement and PCI > 12.

  3. Trimegestone in a low-dose, continuous-combined hormone therapy regimen prevents bone loss in osteopenic postmenopausal women

    DEFF Research Database (Denmark)

    Warming, Lise; Ravn, Pernille; Spielman, Danièle

    2004-01-01

    bone-specific alkaline phosphatase revealed a more retarded decrease of 40% and 33%, respectively. Of the women receiving hormone therapy, 75% had amenorrhea from the first cycle, and 5% withdrew prematurely due to metrorrhagia or mastalgia. CONCLUSION: This new estrogen + progestogen therapy...

  4. Effect of a novel bladder preservation therapy, BOAI-CDDP-radiation (OMC-regimen).

    Science.gov (United States)

    Azuma, Haruhito; Inamoto, Teruo; Takahara, Kiyoshi; Nomi, Hayahito; Uehara, Hiroshi; Komura, Kazumasa; Minami, Koichiro; Kouno, Junko; Kotake, Yatsugu; Abe, Hirokazu; Takagi, Shizuko; Yamamoto, Kazuhiro; Narumi, Yoshihumi; Kiyama, Satoshi

    2013-07-01

    We have developed a novel form of bladder preservation therapy [OMC (Osaka Medical College)-regimen] involving balloon-occluded-arterial-infusion (BOAI) of an anticancer agent (cisplatin/gemcitabine), used concomitantly with hemodialysis, which delivers an extremely high concentration of anticancer agent to the site of a tumor without systemic adverse effects, along with concurrent radiation. We previously reported that the OMC-regimen elicited a complete response (CR) in >90% of patients with organ confined tumors, while LN(+), T4 tumors and a non-UC histological type were statistically significant risk factors for treatment failure and patient survival. In this study, we investigated the effects of the OMC-regimen in patients with organ confined urothelial cancer tumors and the outcomes were compared to those with total cystectomy. Three hundred and one patients were assigned to receive either the OMC-regimen (n=162) or total cystectomy (n=139). Patients in the OMC-regimen group who failed to achieve CR underwent cystectomy, or secondary BOAI with an increased amount of CDDP or gemcitabine (1600 mg). The OMC-regimen yielded 98.1% of clinical response; CR in 93.8% (152/162) of patients; PR in 4.3% (7/162). More than 96% of the CR patients (146/152) were alive with no evidence of recurrence after a mean follow-up of 166 (range 23-960) weeks. No patients suffered grade III toxicity; all patients successfully completed this therapy. The patient survival was significantly better compared to the cystectomy group; the overall 5-, 10- and 15-year survival rates were 87.3, 79.6 and 59.7%, respectively. Moreover, the 5-, 10- and 15-year bladder intact survival rates, the most important issue for bladder preservation therapy, were 85.7, 78.4 and 58.8%, respectively. In conclusion, the OMC-regimen is a useful bladder-preservation strategy, not only in those for whom cystectomy is indicated, but also in patients whose condition is not amenable to curative treatment and for

  5. Oral combination chemotherapy in the treatment of AIDS ...

    African Journals Online (AJOL)

    Objectives: To determine the effectiveness of an oral combination chemotherapy regimen administered to patients with AIDS-associated Hodgkin's disease. Design: Prospective, pilot phase II clinical trial. Setting: Consecutive patient recruitment occurred at two medical centers in the United States: Albany Medical Center, ...

  6. Insulin use, prescription patterns, regimens and costs.-a narrative from a developing country

    Directory of Open Access Journals (Sweden)

    Ogbera Anthonia O

    2012-12-01

    Full Text Available Abstract Background Achieving good glycemic control is of paramount importance in the reduction of diabetes mellitus (DM associated morbidity and mortality. Insulin plays a key role in the management of DM but unfortunately whilst some healthcare providers present insulin as a treatment of last resort , patients on insulin often have insulin related issues such as needle phobias, fear of hypoglycaemia, weight gain and in developing countries, costs. This Report aims at assessing insulin prescription pattern, insulin costs and issues associated with adherence. Methods This was a Cross-sectional observation Study whereby 160 patients with DM who were on insulin solely or in combination with oral hypoglycaemic agents were recruited over a 6 month period. Information obtained from the Study subjects pertained to their histories of DM, types of insulin, insulin costs, adherence issues and insulin delivery devices. Long and short term glycaemic control were determined and evaluated for possible relation to insulin adherence. Test statistics used were chi square, t test and binary regression. Results Insulin adherence was noted in 123-77% of the Study subjects and this was comparable between persons with type 1 DM and those with type 2 DM. The mean glycosylated haemoglobin values were significantly higher in those who admitted to non insulin adherence compared to those who adhered to their insulin regimen (9.7% (2.3 Vs 8.6% (2.1, p = 0.01. Reasons proffered by Respondents for non insulin adherence included high costs-15(41%, inconvenience −15 (41% and needle pain-7918%. A greater proportion of persons who self injected insulin adhered to insulin prescriptions compared to those who did not self inject and thus had better glycaemic control. Shorter duration of DM and older age were found to be predictors of adherence to insulin prescription. The monthly mean costs of insulin for those who earned an income was 5212.8 Nigerian naira which is

  7. Comparison of different glucocorticoid regimens in the management of classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

    Science.gov (United States)

    Ajish, T P; Praveen, V P; Nisha, B; Kumar, Harish

    2014-11-01

    There are recommendations regarding the total dose of hydrocortisone to be administered in the treatment of classical congenital adrenal hyperplasia (CAH) to achieve the twin objectives of glucocorticoid replacement and control of hyperandrogenism. However, there is evidence gap regarding the breakup, timing and type of the steroid regimen. Efficacy of three different glucocorticoid regimens having the same total dose of steroid, differing in either the timing or type of evening steroid administered, in achieving biochemical control of the disease was assessed. The study was done in 13 prepubertal children with classical CAH over a 6-month period with 2 months devoted to each regimen. We used a prospective cross-over design using 10-15 mg/m(2) total dose of hydrocortisone. Two-fifths of the total dose of hydrocortisone was administered in the morning and one-fifth of the total dose was administered at noon in all the regimens. The regimens differed in the timing of the evening dose of hydrocortisone, 06.00-07.00 pm in regimen 1 and 09.00-10.00 pm in regimen 2. The third regimen had the evening dose of hydrocortisone replaced by an equivalent dose of prednisolone suspension which was administered at 10.00 pm. Serum 17-hydroxyprogesterone and testosterone levels were compared to assess the efficacy of treatment regimens. The three different regimens were found to be similar in their ability to control 17-hydroxyprogesterone and testosterone levels. The percentage of patients with predefined criteria for biochemically controlled disease was similar in all the three regimens. However, there was a trend toward better control of 17-hydroxyprogesterone levels in patients receiving evening dose of prednisolone. There is no significant advantage in administering the hydrocortisone dose late at night in patients with classical CAH.

  8. Safety, efficacy, and patient acceptability of single-dose fosaprepitant regimen for the prevention of chemotherapy-induced nausea and vomiting

    Directory of Open Access Journals (Sweden)

    Celio L

    2013-05-01

    Full Text Available Luigi Celio, Francesca Ricchini, Filippo De BraudMedical Oncology Unit 1, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, ItalyAbstract: Control of chemotherapy-induced nausea and vomiting (CINV is a crucial factor in ensuring that patients undergoing cancer chemotherapy can get the full benefit of therapy. Current antiemetic guidelines recommend that the neurokinin-1 receptor (NK-1R antagonist aprepitant should be used as part of a combination regimen with dexamethasone and a serotonin receptor antagonist for the prevention of CINV in patients receiving highly emetogenic chemotherapy (HEC. Fosaprepitant is a water-soluble N-phosphoryl derivative of aprepitant that, when infused, is rapidly metabolized back to an active aprepitant. The existing literature in PubMed about fosaprepitant was screened and selected in order to address the emerging data from two randomized clinical trials evaluating the efficacy and safety of a single-dose fosaprepitant regimen. These phase III trials demonstrated that fosaprepitant given as a single intravenous dose of 150 mg was either noninferior to the conventional 3-day aprepitant or significantly superior to placebo for the prevention of acute and delayed CINV in patients receiving high-dose cisplatin. In both trials, fosaprepitant was well tolerated although more frequent infusion-site adverse events were observed with fosaprepitant. The new dosage regimen of fosaprepitant, therefore, would be an option for CINV control in patients receiving cisplatin-based chemotherapy. The clinical efficacy is consistent with the findings from a time-on-target, positron-emission tomography study evaluating the NK-1R occupancy in the central nervous system (CNS over 5 days after a single-dose infusion of 150 mg fosaprepitant in healthy participants. The single-dose regimen is capable of blocking more than 90% of the NK-1Rs in the CNS for at least 48 hours after infusion, which is sufficient

  9. Assessment of non-standard HIV antiretroviral therapy regimens at Lighthouse Trust in Lilongwe, Malawi.

    Science.gov (United States)

    Barnett, B S; Chaweza, T; Tweya, H; Ngambi, W; Phiri, S; Hosseinipour, M C

    2016-03-01

    Lighthouse Trust in Lilongwe, Malawi serves approximately 25,000 patients with HIV antiretroviral therapy (ART) regimens standardized according to national treatment guidelines. However, as a referral centre for complex cases, Lighthouse Trust occasionally treats patients with non-standard ART regimens (NS-ART) that deviate from the treatment guidelines. We evaluated factors contributing to the use of NS-ART and whether patients could transition to standard regimens. This was a cross-sectional study of all adult patients at Lighthouse Trust being treated with NS-ART as of February 2012. Patients were identified using the electronic data system. Medical charts were reviewed and descriptive statistics were obtained. One hundred six patients were initially found being treated with NS-ART, and 92 adult patients were confirmed to be on NS-ART after review. Mean patient age was 42.4 ± 10.3 years, and 52 (57%) were female. Mean duration of treatment with the NS-ART being used at the time of data collection was 2.1 ± 1.5 years. Eight patients (9%) were on modified first-line NS-ART and 84 (91%) were on modified second-line NS-ART, with 90 patients (98%) having multiple factors contributing to NS-ART use. Severe toxicity from one medication contributed in 28 cases (30%) and toxicity from multiple medications contributed in 46 cases (50%), while 22 patients (24%) were transitioned to NS-ART following a stockout of their original medication. Following clinical review, 84 patients (91%) were transitioned to standard regimens, and eight (9%) were maintained on NS-ART because of incompatibility of their clinical features with the latest national guidelines. Primary factors contributing to NS-ART use were medication toxicities and medication stockouts. Most patients were transitioned to standard regimens, although the need for NS-ART remains.

  10. Possible impact of the standardized Category IV regimen on multidrug-resistant tuberculosis patients in Mumbai.

    Science.gov (United States)

    Udwadia, Zarir F; Mullerpattan, Jai Bharat; Shah, Kushal D; Rodrigues, Camilla S

    2016-01-01

    Treatment of multidrug-resistant tuberculosis (MDR-TB) in the Programmatic Management of Drug-resistant TB program involves a standard regimen with a 6-month intensive phase and an 18-month continuation phase. However, the local drug resistance patterns in high MDR regions such as Mumbai may not be adequately reflected in the design of the regimen for that particular area. The study was carried out at a private Tertiary Level Hospital in Mumbai in a mycobacteriology laboratory equipped to perform the second-line drug susceptibility testing (DST). We attempted to analyze the impact of prescribing the standardized Category IV regimen to all patients receiving a DST at our mycobacteriology laboratory. All samples confirmed to be MDR-TB and tested for the second-line drugs at Hinduja Hospital's Mycobacteriology Laboratory in the year 2012 were analyzed. A total of 1539 samples were analyzed. Of these, 464 (30.14%) were MDR-TB, 867 (56.33%) were MDR with fluoroquinolone resistance, and 198 (12.8%) were extensively drug-resistant TB. The average number of susceptible drugs per sample was 3.07 ± 1.29 (assuming 100% cycloserine susceptibility). Taking 4 effective drugs to be the cut or an effective regimen, the number of patients receiving 4 or more effective drugs from the standardized directly observed treatment, short-course plus regimen would be 516 (33.5%) while 66.5% of cases would receive 3 or less effective drugs. Our study shows that a high proportion of patients will have resistance to a number of the first- and second-line drugs. Local epidemiology must be factored in to avoid amplification of resistance.

  11. Dissolved oxygen regimen (PO2 may affect osmorespiratory compromise in European sea bass (Dicentrarchus labrax, L.

    Directory of Open Access Journals (Sweden)

    Genciana Terova

    2010-02-01

    Full Text Available Fundamentally, in land based mediterranean aquaculture, two techniques are applied to supply water with oxygen: paddling water aeration and application of pure oxygen. The two oxygenation techniques result in quite different PO2 regimens and, consequently, different fish growth performance and gill morphology. Data exist showing a reduction in total respiratory surface (RSA and increasing gas diffusion distance (GDD in gills of sea bass (Dicentrarchus labrax, L. farmed under elevated PO2 regimens. That such a modification might have an effect on the ion regulation has been defined elsewhere as osmorespiratory compromise. In this study, European sea bass previously acclimatized to two PO2 regimens, mild hypoxia and mild hyperoxia (70-80% and 130-140% of the saturation value, respectively, were challenged for 1 hour with hypo-osmotic plus manipulation stress in two separate trials. During the first trial, when only Na+ loss was determined, the ion efflux during the first 5 min resulted in a rate of 163.72±31 and 112.23±87 nmol g-1min-1 from hypoxia and hyperoxia sea bass groups, respectively, and, if sustained, would approach 15.3 and 11.2% per hour of the total body Na+, respectively. During the second trial, in which both Na+ and Cl- loss were determined, after 60 min the Na+ loss was shown to be 76.86±12 and 179.28±32 nmol g-1 min-1 for the fish previously acclimatized to hyperoxia and hypoxia regimens, respectively, whereas for Cl- this loss was 62.02±11 and 157.28±28 nmol g-1min-1, respectively. Our data are compatible with the hypothesis of an osmotic advantage of sea bass exposed to an elevated PO2 regimen, achievable with application of pure oxygen, instead of simple water aeration.

  12. Nitazoxanide Use as Part of an Empiric Multi-Drug Regimen in Treating Children with Suspected Helicobacter pylori Infection

    Directory of Open Access Journals (Sweden)

    Asuncion G. Ramos-Soriano

    2015-01-01

    Full Text Available Helicobacter pylori, a Gram-negative bacterium found in the human stomach, is often present in patients with chronic gastritis. Traditional treatment for H. pylori infection includes metronidazole or clarithromycin, both being associated with development of resistance. In this retrospective report, we describe our clinical experience using a multi-drug treatment regimen for pediatric H. pylori that included nitazoxanide, a newer nitrothiazole benzamide compound used in treating intestinal protozoa infections. Charts were identified for patients who were treated between January 1, 2008 and December 31, 2013 with an ICD-9-CM code 041.86 (H. pylori and who underwent elective endoscopy. All patients were exposed to nitazoxanide for 3 days plus azithromycin, and cefixime (or another 3rd-generation oral cephalosporin for 7-10 days, plus a proton pump inhibitor for 30 days. The clinical cure criteria were predefined. There were 127 individual occurrences or cases identified for inclusion in the review, with 111 occurrences meeting the inclusion criteria. The success rate or clinical cure for the new therapy combination prescribed as defined prior to the chart review was 99 out of 111 cases (89.2%. There were no serious adverse events observed or reported during the treatment of any patient. Approximately 10% of patient charts reflected minor complaints of nausea, vomiting or abdominal cramps during the time of active drug therapy. Nitazoxanide appears to be an effective and well-tolerated option for use in combination with other agents to treat H. pylori-induced gastritis.

  13. Addition of Arsenic Trioxide into Induction Regimens Could Not Accelerate Recovery of Abnormality of Coagulation and Fibrinolysis in Patients with Acute Promyelocytic Leukemia.

    Directory of Open Access Journals (Sweden)

    Ye Zhang

    Full Text Available All-trans retinoic acid combined to anthracycline-based chemotherapy is the standard regimen of acute promyelocytic leukemia. The advent of arsenic trioxide has contributed to improve the anti-leukemic efficacy in acute promyelocytic leukemia. The objectives of the current study were to evaluate if dual induction by all-trans retinoic acid and arsenic trioxide could accelerate the recovery of abnormality of coagulation and fibrinolysis in patients with acute promyelocytic leukemia.Retrospective analysis was performed in 103 newly-diagnosed patients with acute promyelocytic leukemia. Hemostatic variables and the consumption of component blood were comparably analyzed among patients treated by different induction regimen with or without arsenic trioxide.Compared to patients with other subtypes of de novo acute myeloid leukemia, patients with acute promyelocytic leukemia had lower platelet counts and fibrinogen levels, significantly prolonged prothrombin time and elevated D-dimers (P<0.001. Acute promyelocytic leukemia patients with high or intermediate risk prognostic stratification presented lower initial fibrinogen level than that of low-risk group (P<0.05. After induction treatment, abnormal coagulation and fibrinolysis of patients with acute promyelocytic leukemia was significantly improved before day 10. The recovery of abnormal hemostatic variables (platelet, prothrombin time, fibrinogen and D-dimer was not significantly accelerated after adding arsenic trioxide in induction regimens; and the consumption of transfused component blood (platelet and plasma did not dramatically change either. Acute promyelocytic leukemia patients with high or intermediate risk prognostic stratification had higher platelet transfusion demands than that of low-risk group (P<0.05.Unexpectedly, adding arsenic trioxide could not accelerate the recovery of abnormality of coagulation and fibrinolysis in acute promyelocytic leukemia patients who received all

  14. Explorations of combinational therapy in cancer : targeting the tumor and its microenvironment by combining chemotherapy with chemopreventive approaches

    NARCIS (Netherlands)

    Wijngaarden, Johannes Willem van

    2011-01-01

    One of the most effective anticancer therapy still remains chemotherapy, however, both used as single agent as in combinational regimens, chemotherapy still encounters the problem of therapeutic resistance. Limitations of chemotherapy have led to the exploration of alternative anti-cancer approaches

  15. Population-based effectiveness and safety of different antiplatelet regimens as secondary prevention for ischemic stroke/Transient ischemic attack

    NARCIS (Netherlands)

    Noorsyahdy, Alfi; De Boer, Anthonius; Deneer, Vera H.M.; Ten Berg, Jurrien M.; Souverein, Patrick C.; Klungel, Olaf H.

    2016-01-01

    Background: Different antiplatelet regimens are used for secondary prevention after ischemic stroke (IS)/transient ischemic attack (TIA), but studies on the relative effectiveness and safety of each regimen in daily practice are lacking. Objectives: To assess the relative effectiveness and safety of

  16. The Role of Health Beliefs in the Regimen Adherence and Metabolic Control of Adolescents and Adults with Diabetes Mellitus.

    Science.gov (United States)

    Brownlee-Duffeck, Martha; And Others

    1987-01-01

    Examined the role of health beliefs in diabetic regimen adherence and metabolic control. Health beliefs accounted for a statistically significant portion of the variance in both. For older patients perceived benefits of adhering to the diabetic regimen was most significant. For younger patients costs figured prominently in adherence and perceived…

  17. A rare phenomenon of atypical lipodystrophy in a patient on HAART in the absence of a protease inhibitor regimen

    Directory of Open Access Journals (Sweden)

    Mohammed Mitha

    2010-11-01

    Full Text Available Lipodystrophy is a complication of patients on antiretroviral (ARV medication; however, it is commonest in patients on long-term treatment and those on protease inhibitor (PI regimens.1,2 We present a rare case of atypical lipodystrophy, presenting as multiple subcutaneous lipomas, in a patient who had been on a non-PI ART regimen for 6 weeks.

  18. Association of Hypoglycemic Treatment Regimens With Cardiovascular Outcomes in Overweight and Obese Subjects With Type 2 Diabetes

    DEFF Research Database (Denmark)

    Ghotbi, Adam Ali; Køber, Lars; Finer, Nick

    2013-01-01

    To assess the association of hypoglycemic treatment regimens with cardiovascular adverse events and mortality in a large population of type 2 diabetic patients at increased cardiovascular risk.......To assess the association of hypoglycemic treatment regimens with cardiovascular adverse events and mortality in a large population of type 2 diabetic patients at increased cardiovascular risk....

  19. Evolution of drug resistance in HIV infected patients remaining on a virologically failing cART regimen

    DEFF Research Database (Denmark)

    Cozzi-Lepri, A; Phillips, AN; Ruiz, L

    2007-01-01

    OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points...

  20. A Simplified 4-Site Economical Intradermal Post-Exposure Rabies Vaccine Regimen: A Randomised Controlled Comparison with Standard Methods

    Science.gov (United States)

    Warrell, Mary J.; Riddell, Anna; Yu, Ly-Mee; Phipps, Judith; Diggle, Linda; Bourhy, Hervé; Deeks, Jonathan J.; Fooks, Anthony R.; Audry, Laurent; Brookes, Sharon M.; Meslin, François-Xavier; Moxon, Richard; Pollard, Andrew J.; Warrell, David A.

    2008-01-01

    Background The need for economical rabies post-exposure prophylaxis (PEP) is increasing in developing countries. Implementation of the two currently approved economical intradermal (ID) vaccine regimens is restricted due to confusion over different vaccines, regimens and dosages, lack of confidence in intradermal technique, and pharmaceutical regulations. We therefore compared a simplified 4-site economical PEP regimen with standard methods. Methods Two hundred and fifty-four volunteers were randomly allocated to a single blind controlled trial. Each received purified vero cell rabies vaccine by one of four PEP regimens: the currently accepted 2-site ID; the 8-site regimen using 0.05 ml per ID site; a new 4-site ID regimen (on day 0, approximately 0.1 ml at 4 ID sites, using the whole 0.5 ml ampoule of vaccine; on day 7, 0.1 ml ID at 2 sites and at one site on days 28 and 90); or the standard 5-dose intramuscular regimen. All ID regimens required the same total amount of vaccine, 60% less than the intramuscular method. Neutralising antibody responses were measured five times over a year in 229 people, for whom complete data were available. Findings All ID regimens showed similar immunogenicity. The intramuscular regimen gave the lowest geometric mean antibody titres. Using the rapid fluorescent focus inhibition test, some sera had unexpectedly high antibody levels that were not attributable to previous vaccination. The results were confirmed using the fluorescent antibody virus neutralisation method. Conclusions This 4-site PEP regimen proved as immunogenic as current regimens, and has the advantages of requiring fewer clinic visits, being more practicable, and having a wider margin of safety, especially in inexperienced hands, than the 2-site regimen. It is more convenient than the 8-site method, and can be used economically with vaccines formulated in 1.0 or 0.5 ml ampoules. The 4-site regimen now meets all requirements of immunogenicity for PEP and can be

  1. A simplified 4-site economical intradermal post-exposure rabies vaccine regimen: a randomised controlled comparison with standard methods.

    Directory of Open Access Journals (Sweden)

    Mary J Warrell

    2008-04-01

    Full Text Available The need for economical rabies post-exposure prophylaxis (PEP is increasing in developing countries. Implementation of the two currently approved economical intradermal (ID vaccine regimens is restricted due to confusion over different vaccines, regimens and dosages, lack of confidence in intradermal technique, and pharmaceutical regulations. We therefore compared a simplified 4-site economical PEP regimen with standard methods.Two hundred and fifty-four volunteers were randomly allocated to a single blind controlled trial. Each received purified vero cell rabies vaccine by one of four PEP regimens: the currently accepted 2-site ID; the 8-site regimen using 0.05 ml per ID site; a new 4-site ID regimen (on day 0, approximately 0.1 ml at 4 ID sites, using the whole 0.5 ml ampoule of vaccine; on day 7, 0.1 ml ID at 2 sites and at one site on days 28 and 90; or the standard 5-dose intramuscular regimen. All ID regimens required the same total amount of vaccine, 60% less than the intramuscular method. Neutralising antibody responses were measured five times over a year in 229 people, for whom complete data were available.All ID regimens showed similar immunogenicity. The intramuscular regimen gave the lowest geometric mean antibody titres. Using the rapid fluorescent focus inhibition test, some sera had unexpectedly high antibody levels that were not attributable to previous vaccination. The results were confirmed using the fluorescent antibody virus neutralisation method.This 4-site PEP regimen proved as immunogenic as current regimens, and has the advantages of requiring fewer clinic visits, being more practicable, and having a wider margin of safety, especially in inexperienced hands, than the 2-site regimen. It is more convenient than the 8-site method, and can be used economically with vaccines formulated in 1.0 or 0.5 ml ampoules. The 4-site regimen now meets all requirements of immunogenicity for PEP and can be introduced without further

  2. Effectiveness of Antiretroviral Therapy in Individuals Who for Economic Reasons Were Switched From a Once-Daily Single-Tablet Regimen to a Triple-Tablet Regimen

    DEFF Research Database (Denmark)

    Engsig, Frederik N; Gerstoft, Jan; Helleberg, Marie

    2014-01-01

    BACKGROUND: To assess the impact on virological outcomes of a switch from branded single-tablet regimen (STR) including tenofovir, efavirenz, and emtricitabine (STR-TEE) to generic triple-tablet regimen (TTR), including tenofovir, efavirenz, and lamivudine (TTR-TEL), which was implemented on April...... April 1, 2011 to March 31, 2012 (n = 56) and cART-experienced HIV patients who were on STR-TEE from April 1, 2010 (n = 356) or were switched from STR-TEE to TTR-TEL after April 1, 2011 (n = 512). We estimated the fraction with detectable HIV-RNA, development of the 184V/I resistance mutations, and time...... to switch of cART. Approximately 96.2% of cART-experienced patients on STR-TEE were shifted to TTR-TEL after April 1, 2011. For the naive STR-TEE and TTR-TEL patients, the fractions with detectable HIV-RNA at week 48 were 7.0% and 8.3% and for the cART experienced 4.0% and 4.4%, respectively. The 184V...

  3. Combination vaccines

    Directory of Open Access Journals (Sweden)

    David AG Skibinski

    2011-01-01

    Full Text Available The combination of diphtheria, tetanus, and pertussis vaccines into a single product has been central to the protection of the pediatric population over the past 50 years. The addition of inactivated polio, Haemophilus influenzae, and hepatitis B vaccines into the combination has facilitated the introduction of these vaccines into recommended immunization schedules by reducing the number of injections required and has therefore increased immunization compliance. However, the development of these combinations encountered numerous challenges, including the reduced response to Haemophilus influenzae vaccine when given in combination; the need to consolidate the differences in the immunization schedule (hepatitis B; and the need to improve the safety profile of the diphtheria, tetanus, and pertussis combination. Here, we review these challenges and also discuss future prospects for combination vaccines.

  4. The safety and contraceptive efficacy of a 24-day low-dose oral contraceptive regimen containing gestodene 60 microg and ethinylestradiol 15 microg.

    Science.gov (United States)

    1999-11-01

    The safety and contraceptive efficacy of a new 24-day regimen of an oral contraceptive combination containing gestodene (GTD) 60 microg and ethinylestradiol (EE) 15 microg was evaluated in an open-label, multicenter study. Adult women received GTD 60 microg/EE 15 microg from day 1 to 24 and 4 days of placebo during a 28-day cycle for either 13 or 19 cycles. Of the 1515 subjects enrolled, 1496 were included in the intent-to-treat analysis. A total of three pregnancies were reported during the 18 194 treatment cycles of the study, yielding a Pearl index of 0.21. Life-table analysis, based on 16 954 cycles, gave an accidental pregnancy rate of 0.0033. The most frequent adverse events were headache (reported in 35% of subjects), absence of bleeding (16%), flu-like syndrome (15%), pharyngitis (15%) and abdominal pain (15%). The most frequent reasons for withdrawal from the study were metrorrhagia, flu syndrome and absence of bleeding. Analyses of withdrawal and intermenstrual bleeding and spotting indicated acceptable cycle control. The 24-day GTD 60 microg/EE 15 microg regimen appears to be a well-tolerated and effective method for low-dose oral contraception. The current formulation offers an ultra-low steroidal dosage combined with a reduced pill-free interval to improve contraceptive efficacy.

  5. High-dose vincristine, fractionated total-body irradiation and cyclophosphamide as conditioning regimen in allogeneic and autologous bone marrow transplantation for childhood acute lymphoblastic leukaemia in second remission: a 7-year Italian multicentre study

    Energy Technology Data Exchange (ETDEWEB)

    Uderzo, C. [Milan Univ. (Italy); Rondelli, R.; Dini, G. [Bologna Univ. (Italy)] [and others

    1995-04-01

    We investigated the feasibility and efficacy of high-dose vincristine (4 mg/m{sup 2} over 4 d) combined with fractionated total body irradiation (F-TBI) (200 cGy x 2 over 3 d) and cyclophosphamide (60 mg/kg for 2 d) as a preparative regimen in allogeneic (AlloBMT) and autologous (ABMT) bone marrow transplantation for 75 consecutive children (median age at transplant 8.5 years) with acute lymphoblastic leukaemia in second complete remission (CR). Median duration of first CR was 26 and 25 months in the AlloBMT and ABMT group, respectively. We conclude that the conditioning regimen with high-dose vincrostine combined with cyclophosphamide and F-TBI is feasible and promising although its therapeutic advantage should be tested in larger series of patients enrolled in randomized studies. (author).

  6. Effect of different cleaning regimens on the adhesion of resin to saliva-contaminated ceramics.

    Science.gov (United States)

    Aladağ, Akın; Elter, Bahar; Çömlekoğlu, Erhan; Kanat, Burcu; Sonugelen, Mehmet; Kesercioğlu, Atilla; Özcan, Mutlu

    2015-02-01

    The aim of this study was to evaluate the influence of different cleaning regimens on the microshear bond strength (μSBS) of three different all-ceramic surfaces after saliva contamination. Cubic ceramic specimens (3 × 3 × 3 mm(3) ) were prepared from three types of ceramics: zirconium dioxide (Z), leucite-reinforced glass ceramic (E), lithium disilicate glass ceramic (EX; n = 12/subgroup). A total of 144 composite resin cylinders (diameter: 1 mm, height: 3 mm) were prepared. Three human-saliva-contaminated surfaces of ceramic specimens were cleaned with either water spray (WS), with 0.5% sodium hypochlorite solution (HC), or with a cleaning paste (CP). Control surface (C) was not contaminated or cleaned. Composite cylinders were bonded to each surface with a resin luting cement. All specimens were stored at 37°C in deionized water until fracture testing. μSBS tests were performed in a universal testing machine (0.5 mm/min), and the results (MPa ± SD) were statistically analyzed (two-way ANOVA, Bonferroni a = 0.05). Fractured surfaces were analyzed to identify the failure types using an optical microscope at 50× magnification. Two representative specimens from all groups were examined with scanning electron microscopy. μSBS test results were significantly affected by the saliva cleaning regimens (p = 0.01) and the ceramic types (p = 0.03). The interaction terms between the ceramic type and saliva cleaning regimen were also significant (p 0.05). In the EX group, C resulted in significantly higher μSBS values (32.6 ± 7.4) than CP (17.4 ± 8.9), WS (15.6 ± 7.3), and HC (14.3 ± 4.5) (p resin were observed in the E and EX groups, whereas only adhesive failures were seen in zirconia groups for all surface treatments. Different ceramic surface cleaning regimens after saliva contamination of the zirconium dioxide revealed μSBS similar to the control group, whereas all surface cleaning regimens tested significantly decreased the bond strength values in the

  7. Combined oral contraceptives versus levonorgestrel for emergency contraception.

    Science.gov (United States)

    Strayer, S M; Couchenour, R L

    1998-12-01

    A study supported by the World Health Organization's Task Force on Postovulatory Methods of Fertility Control compared the efficacy of the Yuzpe and levonorgestrel-only methods of emergency contraception (EC). Enrolled in this double-blind, randomized trial were 1998 women from 21 centers around the world who requested EC within 72 hours of unprotected intercourse. The pregnancy rate was 1.1% for levonorgestrel alone and 3.2% for the combined ethinyl estradiol-levonorgestrel regimen. The crude relative risk of pregnancy was 0.36 (95% confidence interval, 0.18-0.70) for levonorgestrel compared with the Yuzpe regimen. The former method prevented 85% of expected pregnancies, while the latter prevented only 57%. Finally, side effects such as nausea, vomiting, dizziness, and fatigue were significantly less common in the levonorgestrel group. Although these findings document the superiority of the levonorgestrel regimen for EC, the 0.75 mg tablets are not currently manufactured in the US.

  8. Pediatric-Inspired Treatment Regimens for Adolescents and Young Adults With Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia: A Review.

    Science.gov (United States)

    Siegel, Stuart E; Stock, Wendy; Johnson, Rebecca H; Advani, Anjali; Muffly, Lori; Douer, Dan; Reed, Damon; Lewis, Mark; Freyer, David R; Shah, Bijal; Luger, Selina; Hayes-Lattin, Brandon; Jaboin, Jerry J; Coccia, Peter F; DeAngelo, Daniel J; Seibel, Nita; Bleyer, Archie

    2018-02-15

    The incidence of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adolescent and young adult (AYA) patients (age range, 15-39 years) in the United States is increasing at a greater rate than in younger or older persons. Their optimal treatment has been increasingly debated as pediatric regimens have become more widely used in the age group. This review compares the basic features of pediatric and adult chemotherapy regimens for ALL and LBL, recognizes and describes the challenges of the pediatric regimen, and suggests strategies to facilitate its adoption for AYAs with ALL and LBL. All but 2 of 25 published comparisons of outcomes with pediatric and adult regimens for ALL and LBL in AYAs and 1 meta-analysis favor the pediatric regimen. After more than a half-century of clinical trials of the pediatric regimens, including at least 160 phase 3 trials in the United States, the pediatric regimens have become far more complex than most adult regimens. Asparaginase, a critical component of the pediatric regimens, is more difficult to administer to AYAs (and older patients) but nonetheless has a favorable benefit to toxicity ratio for AYAs. A dramatic reduction in outcome of ALL and LBL during the AYA years (the "survival cliff") is coincident with similar reductions in proportions of AYAs referred to academic centers and enrolled on clinical trials (the "accrual cliff" and "referral cliff"). The accumulating data increasingly support treating AYAs with ALL and LBL with a pediatric-inspired regimen or an approved institutional or national clinical trial tailored for this patient group. A need to develop clinical trials specifically for AYAs and to encourage their participation is paramount, with a goal to improve both the quantity and quality of survival.

  9. Immunologic changes in TNF-alpha, sE-selectin, sP-selectin, sICAM-1, and IL-8 in pediatric patients treated for psoriasis with the Goeckerman regimen

    Energy Technology Data Exchange (ETDEWEB)

    Borska, L.; Fiala, Z.; Krejsek, J.; Andrys, C.; Vokurkova, D.; Hamakova, K.; Kremlacek, J.; Ettler, K. [Charles University of Prague, Hradec Kralove (Czech Republic). Faculty of Medicine

    2007-11-15

    Psoriasis is a chronic inflammatory skin disease which is often manifested during childhood. The present study investigated changes in the serum levels of proinflammatory cytokines and soluble forms of adhesion molecules in children with psoriasis. The observed patient group of 26 children was treated with the Goeckerman regimen. This therapy combines dermal application of crude coal tar with ultraviolet radiation. The Psoriasis Area Severity Index decreased significantly after treatment by with the Goeckerman regimen (p < 0.001). Serum levels of the proinflammatory cytokine TNF-alpha and adhesion molecules sICAM-1, sP-selectin and sE-selectin decreased after the Goeckerman regimen. The TNF-alpha and sICAM-1 decreased significantly (p < 0.05). Our findings support the complex role of these immune parameters in the immunopathogenesis of psoriasis in children. The serum level of IL-8 increased after the Goeckerman regimen. This fact indicates that the chemokine pathway of IL-8 activity could be modulated by this treatment, most likely by polycyclic aromatic hydrocarbons.

  10. Preclinical optimization of a broad-spectrum anti-bladder cancer tri-drug regimen via the Feedback System Control (FSC) platform

    Science.gov (United States)

    Liu, Qi; Zhang, Cheng; Ding, Xianting; Deng, Hui; Zhang, Daming; Cui, Wei; Xu, Hongwei; Wang, Yingwei; Xu, Wanhai; Lv, Lei; Zhang, Hongyu; He, Yinghua; Wu, Qiong; Szyf, Moshe; Ho, Chih-Ming; Zhu, Jingde

    2015-06-01

    Therapeutic outcomes of combination chemotherapy have not significantly advanced during the past decades. This has been attributed to the formidable challenges of optimizing drug combinations. Testing a matrix of all possible combinations of doses and agents in a single cell line is unfeasible due to the virtually infinite number of possibilities. We utilized the Feedback System Control (FSC) platform, a phenotype oriented approach to test 100 options among 15,625 possible combinations in four rounds of assaying to identify an optimal tri-drug combination in eight distinct chemoresistant bladder cancer cell lines. This combination killed between 82.86% and 99.52% of BCa cells, but only 47.47% of the immortalized benign bladder epithelial cells. Preclinical in vivo verification revealed its markedly enhanced anti-tumor efficacy as compared to its bi- or mono-drug components in cell line-derived tumor xenografts. The collective response of these pathways to component drugs was both cell type- and drug type specific. However, the entire spectrum of pathways triggered by the tri-drug regimen was similar in all four cancer cell lines, explaining its broad spectrum killing of BCa lines, which did not occur with its component drugs. Our findings here suggest that the FSC platform holdspromise for optimization of anti-cancer combination chemotherapy.

  11. A randomized open-labeled study to demonstrate the non-inferiority of purified chick-embryo cell rabies vaccine administered in the Zagreb regimen (2-1-1) compared with the Essen regimen in Chinese adults.

    Science.gov (United States)

    Ma, Jingchen; Wang, Hongchang; Li, Jun; Chang, Likuan; Xie, Yun; Liu, Zhonglin; Zhao, Yuliang; Malerczyk, Claudius; Claudius, Malerczyk

    2014-01-01

    The Zagreb regimen has been used for 20 years in various countries. In China, until 2010, the Zagreb schedule was only approved for purified chick embryo cell vaccine (PCECV) and purified Vero cell rabies vaccines (PVRV). In this phase III clinical trial, we aimed to demonstrate the safety and immunogenic non-inferiority of the Zagreb regimen compared with the Essen regimen in healthy adult Chinese immunized with PCECV (Rabipur®). The study enrolled 825 subjects aged 18 to 50 years; serum samples were collected on Days 0, 7, 14, 42, and at 13 months to assess rabies virus neutralizing antibody (RVNA) concentrations. Solicited and unsolicited local and systemic reactions were recorded for 6 days following the day of vaccination, and collected throughout the entire study period (Day 1 until Month 13). The Zagreb regimen was non-inferior to the Essen regimen with regard to RVNA concentrations after 7, 14, and 42 days, and 13 months of immunization. The non-inferiority of seroconversion was established at Days 14 and 42. The incidence of local and systemic reactions was similar between groups, and mostly of mild or moderate severity. Vaccine-related adverse events occurred more frequently in the Essen group than in the Zagreb group. Vaccination with PCECV under a 2-1-1 regimen is as safe and immunogenic as under the traditional 5-dose Essen regimen for rabies post-exposure prophylaxis, and is a more cost-effective option, has a more practical vaccination schedule, and can potentially increase compliance.

  12. Etoposide-containing conditioning regimen reduces the occurrence of hemophagocytic lymphohistiocytosis after SCT.

    Science.gov (United States)

    Kobayashi, R; Tanaka, J; Hashino, S; Ota, S; Torimoto, Y; Kakinoki, Y; Yamamoto, S; Kurosawa, M; Hatakeyama, N; Haseyama, Y; Sakai, H; Sato, K; Fukuhara, T

    2014-02-01

    Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages that secrete high amounts of inflammatory cytokines. HLH occurring after SCT is difficult to diagnose. It is characterized by severe clinical manifestations and high mortality. Despite current therapeutic approaches, outcomes remain poor. We analyzed the incidence and risk factors of HLH after SCT and the response to treatment and prognosis of 554 patients with HLH after SCT. The cumulative incidence of HLH after SCT was 4.3% (24/554). Use of etoposide in the conditioning regimen was only factor that reduced HLH after SCT (P=0.027). All patients who received autologous transplantation were successfully treated. Patients with liver dysfunction (for example, high total bilirubin level, prolonged prothrombin time and high level of fibrinogen degradation products) had a poor response to treatment for HLH. Physicians should be cautious of HLH, while not using etoposide for conditioning regimen.

  13. Triple Active Antiretroviral Regimen Including Enfuvirtide Via the Biojector is Effective and Safe

    Directory of Open Access Journals (Sweden)

    Mona Loutfy

    2007-01-01

    Full Text Available For full HIV virological suppression, three fully active antiretroviral agents are required. New drug classes should be included to ensure that agents are fully active. The addition of enfuvirtide and efavirenz to the present patient’s new antiretroviral regimen ensured that two fully active agents were in use in the setting of a moderate degree of nucleoside resistance and a high level of protease resistance, and where non-nucleoside reverse transcriptase inhibitors were still fully active. Both viral load and CD4 count responded favourably to this regimen. The patient received support from physicians and clinic staff in the introduction and use of enfuvirtide. To reduce injection site reactions, a needle-free injection system (Biojector proved effective.

  14. Modified Colistin Regimen for Critically Ill Patients with Acute Renal Impairment and Continuous Renal Replacement Therapy.

    Science.gov (United States)

    Menna, Pierantonio; Salvatorelli, Emanuela; Mattei, Alessia; Cappiello, Dario; Minotti, Giorgio; Carassiti, Massimiliano

    2018-01-01

    Colistin is a last resort antibiotic to treat multidrug-resistant Gram-negative bacteria infections. Colistin is administered intravenously in the form of its inactive prodrug colistin methanesulfonate (CMS). For patients with acute kidney impairment and continuous renal replacement therapy high extracorporeal clearance may cause a substantial removal of active colistin from the bloodstream, eventually decreasing its antibacterial efficacy. Currently recommended doses of CMS may therefore be inadequate for these patients. We report on the potential value of a modified regimen that adopts a loading dose of CMS (bolus of 9 MU vs. conventional 3 MU every 8 h), followed by maintenance (3 MU every 8 h). Preliminary pharmacokinetic evidence for the feasibility and efficacy of this regimen is described for 2 patients. © 2017 S. Karger AG, Basel.

  15. Behavioral economics as a promising framework for promoting treatment adherence to pediatric regimens.

    Science.gov (United States)

    Stevens, Jack

    2014-01-01

    To summarize previous adult research on behavioral economics (BE) and consider the largely unexplored relevance of BE for promoting adherence to pediatric regimens across a wide variety of illnesses. Literature review. Default bias, loss aversion, overestimation of rare events, and social norms are four BE concepts that have not been fully incorporated in adherence research for pediatric regimens yet offer promising opportunities for novel intervention development. The possible applications of these four strategies are offered in regards to asthma, cystic fibrosis, migraines, and diabetes, respectively.  BE offers pediatric psychology not only low-intensity approaches for promoting adherence but also highly attractive ways of obtaining the attention of health care administrators and policymakers. © The Author 2014. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Modelling and analysis of the feeding regimen induced entrainment of hepatocyte circadian oscillators using petri nets.

    Directory of Open Access Journals (Sweden)

    Samar Hayat Khan Tareen

    Full Text Available Circadian rhythms are certain periodic behaviours exhibited by living organism at different levels, including cellular and system-wide scales. Recent studies have found that the circadian rhythms of several peripheral organs in mammals, such as the liver, are able to entrain their clocks to received signals independent of other system level clocks, in particular when responding to signals generated during feeding. These studies have found SIRT1, PARP1, and HSF1 proteins to be the major influencers of the core CLOCKBMAL1:PER-CRY circadian clock. These entities, along with abstracted feeding induced signals were modelled collectively in this study using Petri Nets. The properties of the model show that the circadian system itself is strongly robust, and is able to continually evolve. The modelled feeding regimens suggest that the usual 3 meals/day and 2 meals/day feeding regimens are beneficial with any more or less meals/day negatively affecting the system.

  17. Modelling and Analysis of the Feeding Regimen Induced Entrainment of Hepatocyte Circadian Oscillators Using Petri Nets

    Science.gov (United States)

    Tareen, Samar Hayat Khan; Ahmad, Jamil

    2015-01-01

    Circadian rhythms are certain periodic behaviours exhibited by living organism at different levels, including cellular and system-wide scales. Recent studies have found that the circadian rhythms of several peripheral organs in mammals, such as the liver, are able to entrain their clocks to received signals independent of other system level clocks, in particular when responding to signals generated during feeding. These studies have found SIRT1, PARP1, and HSF1 proteins to be the major influencers of the core CLOCKBMAL1:PER-CRY circadian clock. These entities, along with abstracted feeding induced signals were modelled collectively in this study using Petri Nets. The properties of the model show that the circadian system itself is strongly robust, and is able to continually evolve. The modelled feeding regimens suggest that the usual 3 meals/day and 2 meals/day feeding regimens are beneficial with any more or less meals/day negatively affecting the system. PMID:25789928

  18. Assessment of tobramycin RIA for drug monitoring and dosage regimen. Comparison with other assay technics

    International Nuclear Information System (INIS)

    Takahashi, S.; Shinozaki, K.; Tsujino, D.; Ohhara, H.; Tanaka, Y.; Arai, S.; Someya, K.; Sasaki, Y.

    1983-01-01

    Because of wide range of inter-individual difference of pharmacokinetic parameter, importance of monitoring blood concentration of aminoglycoside antibiotics in each patient has been recognized. With the purpose to use for monitoring of serum tobramycin (TOB) levels and for adequate dosage regimen RIA of TOB was evaluated in comparison with other assay technics. Gamma Coat TOB RIA kits (Clinical Assay-Travenol Japan) were used for RIA of TOB. The TOB concentrations in the same samples were also measured by two kinds of enzyme immunoassay (EIA) (EMIT EIA and SLFIA EIA), High Performance Liquid Chromatography (HPLC) and bioassay (BA). RIA of TOB is a useful assay method with high sensitivity and reasonably good precision to be used for drug monitoring and adequate dosage regimen. Modification of the method for rapid assay of a small number of samples will increase the clinical usefulness in individualized drug monitoring

  19. Study of hypothalamic pituitary adrenal axis in patients of membranous nephropathy receiving modified Ponticelli regimen

    Directory of Open Access Journals (Sweden)

    R Ramachandran

    2015-01-01

    Full Text Available Pulse methyl prednisolone followed by oral prednisolone and abrupt switch to chlorambucil/cyclophosphamide (Ponticelli/modified Ponticelli regimen is used in patients with idiopathic membranous nephropathy. This therapy where steroids are stopped abruptly is unphysiologic and expected to have hypothalamic pituitary adrenal (HPA axis suppression; however, this has not been evaluated. A total of 13 consecutive adult patients with idiopathic membranous nephropathy who had completed modified Ponticelli regimen were studied. The regimen included administration of pulse methylprednisolone 1 g for 3 days followed by oral prednisolone 0.5 mg/kg/day for 27 days followed by oral cyclophosphamide at a dose of 2 mg/kg/day for the next month. This was repeated for three courses. Patients who had received corticosteroids prior to therapy were excluded. The HPA axis was evaluated after 1 month of completing the last course of steroid therapy. The evaluation was done using a low-dose adrenocorticotropic hormone stimulation test. A single intravenous bolus dose of synacthen (1 μg was given at 9.00 am and the serum cortisol levels were estimated by radioimmunoassay at 0, 30, and 60 min. A peak cortisol level of 550 nmol/L or higher was considered as normal. Mean baseline cortisol levels was 662.3 ± 294.6 nmol/L and peak cortisol level was 767 ± 304.4 nmol/L. A total of 6 patients (46.2% had low basal cortisol levels, only 3 (23% had both basal and peak cortisol levels < 550 nmol/L suggestive of HPA axis suppression. To conclude, 23% of patients had suppression of HPA axis after modified Ponticelli regimen.

  20. The Effectiveness of a Working Memory Training Regimen for Iranian University Students: Implications for Medical Students

    OpenAIRE

    Gholam Reza Kiany; Bahman Mehraban; Reza Ghafar Samar

    2016-01-01

    Introduction: Working memory is thought to serve as a part of memory structure where functions like temporary storage and manipulation of information take place. This study investigates the effectiveness of working memory training regimens with Iranian university students, while considering the implications for medical students. Methods: Thirty university students studying at different universities in Kermanshah took part in the study. They were divided into two groups as the experimental...

  1. Modeling of velocity regimens for anaerobic and aerobic power exercises in high-performance swimmers.

    Science.gov (United States)

    Issurin, V B; Kaufman, L E; Tenenbaum, G

    2001-12-01

    This study was aimed at investigating the validity and eligibility of a modeling method to determine velocity regimes of highly intensive swimming exercises. The model postulates that swimming velocity regimens, which correspond to the three biomotor components, i.e.: Maximal Anaerobic Power, Anaerobic Capacity, and Aerobic Power, can be predicted by special equations using a 50 m all out swim velocity, and the equation coefficient, which determine swimmer's classification. The swimmers are classified into 12 categories according to pre-determined race distance records, and swimmer's capability level. Comparative field study was used to contrast predicted velocity regimens with observed velocity regimes. National swimming center at the Wingate Institute for Physical Education. 22 highly trained swimmers (14 male and 8 female) participated in this study and were examined 1-4 times within a period of two years in totally 162 sessions. The 50 m all-out trial was performed and three basic velocity regimens were predicted according to the modeling procedure. Three different interval sets were carried out by all the swimmers for validation procedures. The blood lactate (BLA) samples were taken after test completion. The correlations between the observed and predicted velocities within each of the three tests were very strong. The RM-ANOVA with respect to lactic acid concentration revealed that across the three measures (different tests) BLA concentration was significantly higher in male swimmers than in female swimmers, and highest in butterfly followed by breaststroke, backstroke, and freestyle stroke. The modeling method allows to predict desirable velocity regimes in order to develop the main biomotor components of the swimmers. This procedure is recommended for practice as a non-invasive method for designing desired training regimens.

  2. A new analgesia regimen after (adeno) tonsillectomy in children: a pilot study.

    Science.gov (United States)

    Syed, M I; Magos, T A; Singh, J; Montague, M L

    2016-12-01

    The objective was to ascertain the efficacy of a new analgesic regimen introduced in children undergoing (adeno)tonsillectomy in view of the ban on codeine use in children codeine, albeit one should bear in mind that parental concerns and adverse effects of the drug were seen in a minority of patients (n = 11) and anaesthetists were reluctant to prescribe the drug in cases of severe OSA or associated central apnoeas (n = 7). © 2015 John Wiley & Sons Ltd.

  3. Management of interstitial ectopic pregnancy with intravenous methotrexate: An extended study of a standardised regimen.

    Science.gov (United States)

    Tanaka, Keisuke; Baartz, David; Khoo, Soot Keat

    2015-04-01

    Interstitial ectopic pregnancy is a rare but potentially life threatening condition. Of the three management options for this condition (expectant, medical and surgical treatment) methotrexate therapy in several regimens has been reported to be effective and beneficial. To assess the safety and efficacy of intravenous bolus and infusion of methotrexate with folinic acid rescue for the treatment of interstitial ectopic pregnancy. A retrospective cohort study of women with interstitial ectopic pregnancy treated with methotrexate at the Royal Brisbane and Women's Hospital from April 2000 to December 2012. The treatment regimen comprised of a bolus dose of methotrexate 100 mg followed by 200 mg of methotrexate infusion over 12 h. Four doses of 15 mg oral folinic acid rescue were given post-treatment. Success of methotrexate therapy was confirmed by either a negative serum beta-human chorionic gonadotropin (β-hCG) level or subsequent uneventful pregnancy. Of 33 women with interstitial ectopic pregnancy who were treated with this regimen, 31 (93.9%) were treated successfully, including women with a high β-hCG level up to 106 634 IU/L and the presence of fetal cardiac activity. Minor side effects were documented in three cases. Intravenous methotrexate therapy with folinic acid rescue is well tolerated and highly effective. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  4. Interpretation of indeterminate HIV-1 PCR results are influenced by changing vertical transmission prevention regimens.

    Science.gov (United States)

    Maritz, Jean; Maharaj, Jayshree Narvin; Cotton, Mark Frederic; Preiser, Wolfgang

    2017-10-01

    Suppression of HIV by antiretroviral drugs may be one of the reasons that indeterminate HIV-1 PCR results are obtained from testing HIV-exposed infants. This complicates the early identification of infected infants, potentially delaying initiating treatment early. There is uncertainty as to how different vertical HIV transmission prevention regimens (VTP) affect the rate and predictive value of indeterminate PCR results. To investigate rates of indeterminate PCR results, outcomes of subsequent samples and the predictive value of an indeterminate PCR for a later positive result in the setting of intensifying VTP in the Western Cape province of South Africa. Retrospective laboratory data analysis. Diagnostic PCR data of a public health laboratory from June 2009 to October 2014 was analysed and categorised by South African VTP regimens. First indeterminate HIV-1 PCRs in patients younger than 12 months were linked with follow-up HIV-1 PCRs and/or serological tests. Linked results sets were analysed by PCR amplification characteristics and subsequent patient outcome. Over intensified VTP regimens, the rate of indeterminate and positive PCRs decreased significantly (5.6-3.2% and 2.4-0.4%, respectively; both pHIV PCRs, although decreasing in frequency with Option B+, should be regarded with a high index of suspicion for being representative of true HIV-1 infections. Additional virological testing is required to arrive at a definitive diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Safety of specific immunotherapy using an ultra-rush induction regimen in bee and wasp allergy.

    Science.gov (United States)

    Bożek, Andrzej; Kołodziejczyk, Krzysztof

    2018-02-01

    Specific allergen immunotherapy to Hymenoptera venom (VIT) is a basic treatment for patients allergic to Hymenoptera venom. The aim of the study was to evaluate the safety of an ultra-rush regimen compared with the rush and conventional protocols. In 31 patients with an allergy to bee venom and 82 with an allergy to wasp venom, the allergic adverse reactions during VIT were monitored. Patients were selected based on the criteria established by EAACI (European Academy of Allergy and Clinical Immunology) recommendations. Adverse reactions during the ultra-rush immunotherapy were measured, documented and classified according to the criteria of Mueller. Ultra-rush, rush or conventional protocols of the initial phase VIT using the Venomenhal vaccine (Hal Allergy, Leiden, Netherlands) were conducted. Six (13.7%) patients on the ultra-rush regimen, 5 (14.3%) patients on the rush regimen and 9 (26.5%) on conventional VIT experienced an allergic reaction. There were no associations between the adverse allergic reactions and the following factors: gender, total IgE and allergen-specific IgE to wasp or bee venom before the VIT and cardiological drugs that were used. We found that the ultra-rush protocol (similar to the rush protocol) using the Venomenhal vaccine is safer than the conventional protocol.

  6. Tissue repair capacity and repair kinetics deduced from multifractionated or continuous irradiation regimens with incomplete repair

    International Nuclear Information System (INIS)

    Thames, H.D. Jr.; Peters, L.J.

    1984-01-01

    A model is proposed for cell survival after multiple doses, when the interfraction interval is insufficient for complete Elkind repair. In the limit of ever-increasing number of ever-smaller fractional doses, the model transforms into the accumulation model of survival after continuous irradiation. When adapted to describe tissue responses to isoeffective multifractionated regimens, wherein repair is incomplete, a generalization of the usually linear plot of reciprocal total dose versus dose per fraction is obtained, in which downward curvature is evident. There is an advantage in studying tissue responses to multifractionated regimens with incomplete repair in the interfraction intervals, or continuous exposures at various dose rates since, in addition to determination of repair capacity, there is an estimate of repair kinetics. Results of analyses of previously published data are presented as illustration. Estimated from the response of three acutely responding normal tissues in the mouse (jejunum, colon and bone marrow), repair halftimes ranged from 0.3-0.9 h and values of β/delta were approximately 0.1 Gy -1 . From the response of mouse lung (LD50 for pneumonitis) to multifractionated regimens with incomplete repair, the repair halftime was estimated at 1.5 h and β/delta was 0.27 Gy -1 . In the rat spinal cord β/delta was 0.7 Gy -1 and Tsub(1/2) was 1.5 h. (U.K.)

  7. A comparison of traditional versus contemporary immunosuppressive regimens in pediatric heart recipients.

    Science.gov (United States)

    Marshall, Clement D; Richmond, Marc E; Singh, Rakesh K; Gilmore, Lisa; Beddows, Kim; Chen, Jonathan M; Addonizio, Linda J

    2013-07-01

    To assess the differences in rejection and infection complications between the most common contemporary immunosuppression regimen in pediatric heart transplantation (cytolytic induction, tacrolimus based) and classic triple-therapy (cyclosporine based without induction). We performed a retrospective, historical-control, observational study comparing outcomes in patients who underwent traditional immunosuppression (control group, n = 64) with those for whom the contemporary protocol was used (n = 39). Episodes of rejection, viremia (cytomegalovirus or Epstein-Barr virus), serious bacterial or fungal infections, anemia or neutropenia requiring treatment in the first year after heart transplantation, and 1-year survival were compared between traditional and contemporary immunosuppression groups. The 2 groups were similar with respect to baseline demographics. There were no differences in risk of cytomegalovirus, Epstein-Barr virus, or bacterial or fungal infections in the first year post-transplantation. Patients in the contemporary group were more likely to need therapy for anemia (51% vs 14%, P contemporary protocol patients were rejection-free in the first year post-transplantation (63% vs 41%, P = .03). Overall graft survival was similar between groups (P = .15). A contemporary immunosuppression regimen using tacrolimus, mycophenolate mofetil, and induction was associated with less rejection in the first year, with no difference in the risk of infection but greater risk of anemia and neutropenia requiring treatment. Long-term follow-up on these patients will evaluate the impact of the immunosuppression regimen on survival. Copyright © 2013 Mosby, Inc. All rights reserved.

  8. Evaluation of Blood Regimen on the Survival of Cimex lectularius L. Using Life Table Parameters

    Directory of Open Access Journals (Sweden)

    Edwin G. Rajotte

    2013-06-01

    Full Text Available Knowledge of bed bug development under varying conditions can lead to more sophisticated management techniques. Development rate, age and stage-specific life tables were compared for a laboratory strain (HS and field strain (ECL-05 of bed bug Cimex lectularius L. (Hemiptera: Heteroptera reared on two blood regimens: human or rabbit blood. Harlan and ECL-05 bed bugs reared on human blood had a life expectancy of 207 and 208 days respectively from the egg stage. Egg to adult development of HS bed bugs reared on human blood (~35 days was significantly longer than that of the ECL-05 strain (~33 days in the third, fourth, and fifth instars. The HS and ECL-05 bed bugs reared on rabbit blood had a life expectancy of 149 and 174 days respectively. Egg to adult development time of HS on rabbit blood (~52 days was significantly longer than ECL-05 (~37 days in every instar, and HS total life span was significantly shorter compared to ECL-05. Developmental differences based on strain and blood regimen suggest rabbit blood is an inferior blood source for colony maintenance, and strain has variable effects on bed bug development. Findings suggest that blood regimen should strongly be considered in bed bug colony maintenance.

  9. Delayed rhabdomyolysis with paclitaxel, ifosfamide, carboplatin, and etoposide regimen: a case report.

    Science.gov (United States)

    Sokolova, Alexandra; Chan, Onyee; Ullah, Waqas; Hamdani, Auon Abbas; Anwer, Faiz

    2017-04-11

    High-dose chemotherapy with autologous stem cell rescue is commonly used for the treatment of relapsed germ cell tumors. We report the first case of delayed rhabdomyolysis with paclitaxel, ifosfamide, carboplatin, and etoposide regimen. We report a case of a 21-year-old African-American man diagnosed with relapsed non-seminomatous germ cell tumor who received high-dose chemotherapy with carboplatin and etoposide following TIGER trial arm B off-protocol. His course was complicated by muscle pain and rhabdomyolysis after cycle 4 on day +12 after infusion of autologous stem cells. To the best of our knowledge, this complication has not been reported with this regimen. A differential diagnosis of sepsis and neutropenic fever along with side effects of high-dose chemotherapy were considered, but based on the timing of events, it was concluded that the etiology of rhabdomyolysis is high-dose chemotherapy. Rhabdomyolysis was successfully treated with hydration and did not recur during subsequent cycle 5. Delayed rhabdomyolysis after high-dose chemotherapy with paclitaxel, ifosfamide, carboplatin, and etoposide regimen has not been previously reported and needs to be considered for preventive strategy and prompt diagnosis and treatment to avoid renal complications. Physicians should have a low threshold to check creatine kinase enzymes in patients with unexplained muscle pain or renal insufficiency after high-dose chemotherapy.

  10. Improvement of ALT decay kinetics by all-oral HCV treatment: Role of NS5A inhibitors and differences with IFN-based regimens.

    Science.gov (United States)

    Cento, Valeria; Nguyen, Thi Huyen Tram; Di Carlo, Domenico; Biliotti, Elisa; Gianserra, Laura; Lenci, Ilaria; Di Paolo, Daniele; Calvaruso, Vincenza; Teti, Elisabetta; Cerrone, Maddalena; Romagnoli, Dante; Melis, Michela; Danieli, Elena; Menzaghi, Barbara; Polilli, Ennio; Siciliano, Massimo; Nicolini, Laura Ambra; Di Biagio, Antonio; Magni, Carlo Federico; Bolis, Matteo; Antonucci, Francesco Paolo; Di Maio, Velia Chiara; Alfieri, Roberta; Sarmati, Loredana; Casalino, Paolo; Bernardini, Sergio; Micheli, Valeria; Rizzardini, Giuliano; Parruti, Giustino; Quirino, Tiziana; Puoti, Massimo; Babudieri, Sergio; D'Arminio Monforte, Antonella; Andreoni, Massimo; Craxì, Antonio; Angelico, Mario; Pasquazzi, Caterina; Taliani, Gloria; Guedj, Jeremie; Perno, Carlo Federico; Ceccherini-Silberstein, Francesca

    2017-01-01

    Intracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR. Mathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR. Kinetic-models and Cox-analysis were used to assess determinants of ALT-decay and normalization. HCV-RNA kinetics was biphasic, reflecting a mean effectiveness in blocking viral production >99.8%. The first-phase of viral-decline was faster in patients receiving NS5A-inhibitors compared to TVR+PR or sofosbuvir+simeprevir (pALT-normalization, noted λ, was slower in patients receiving TVR+PR or sofosbuvir+simeprevir compared to NS5A-inhibitors (0.17 vs 0.27 d-1, respectively, pALT normalization rate and, for a given level of viral reduction, ALT-normalization was more profound in patients receiving DAA, and NS5A in particular, than TVR+PR. Our data support a process of HCV-clearance by all-DAA regimens potentiated by NS5A-inhibitor, and less relying upon hepatocyte death than IFN-containing regimens. This may underline a process of "cell-cure" by DAAs, leading to a fast improvement of liver homeostasis.

  11. Review of basal-plus insulin regimen options for simpler insulin intensification in people with Type 2 diabetes mellitus.

    Science.gov (United States)

    Raccah, D; Huet, D; Dib, A; Joseph, F; Landers, B; Escalada, J; Schmitt, H

    2017-09-01

    To identify simple insulin regimens for people with Type 2 diabetes mellitus that can be accepted and implemented earlier in primary and specialist care, taking into consideration each individual's needs and capabilities. Using randomized clinical trials identified by a search of the PubMed database, as well as systematic reviews, meta-analyses and proof-of-concept studies, this review addresses topics of interest related to the progressive intensification of a basal insulin regimen to a basal-plus regimen (one basal insulin injection plus stepwise addition of one to three preprandial short-acting insulin injections/day) vs a basal-bolus regimen (basal insulin plus three short-acting insulin injections per day) in people with Type 2 diabetes. The review explores approaches that can be used to define the meal for first prandial injection with basal-plus regimens, differences among insulin titration algorithms, and the importance of self-motivation and autonomy in achieving optimum glycaemic control. A basal-plus regimen can provide glycaemic control equivalent to that obtained with a full basal-bolus regimen, with fewer injections of prandial insulin. The first critical step is to optimize basal insulin dosing to reach a fasting glucose concentration of ~6.7 mmol/l; this allows ~40% of patients with baseline HbA 1c >75 mmol/mol (9%) to be controlled with only one basal insulin injection per day. Compared with a basal-bolus regimen, a basal-plus insulin regimen is as effective but more practical, and has the best chance of acceptance and success in the real world. © 2017 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

  12. Combination Vaccines

    OpenAIRE

    Skibinski, David AG; Baudner, Barbara C; Singh, Manmohan; O’Hagan, Derek T

    2011-01-01

    The combination of diphtheria, tetanus, and pertussis vaccines into a single product has been central to the protection of the pediatric population over the past 50 years. The addition of inactivated polio, Haemophilus influenzae, and hepatitis B vaccines into the combination has facilitated the introduction of these vaccines into recommended immunization schedules by reducing the number of injections required and has therefore increased immunization compliance. However, the development of th...

  13. Clinical Pharmacokinetics of Levornidazole in Elderly Subjects and Dosing Regimen Evaluation Using Pharmacokinetic/Pharmacodynamic Analysis.

    Science.gov (United States)

    Guo, Beining; He, Gaoli; Wu, Xiaojie; Yu, Jicheng; Cao, Guoying; Li, Yi; Fan, Yaxin; Chen, Yuancheng; Shi, Yaoguo; Zhang, Yingyuan; Zhang, Jing

    2017-07-01

    Levornidazole, the levo-isomer of ornidazole, is a third-generation nitroimidazole derivative newly developed after metronidazole, tinidazole, and ornidazole. An open-label, parallel-controlled, single-dose study was conducted for the investigation of the pharmacokinetic (PK) profile of levornidazole and its metabolites in healthy elderly Chinese subjects, and for the evaluation of 2 dosing regimens in the elderly. Levornidazole was intravenously administered at 500 mg to healthy elderly (aged 60-80 years) or young subjects (aged 19-45 years). The PK profiles of levornidazole and its metabolites in elderly subjects were evaluated and compared with those in the young group. WinNonlin software was used for simulating the PK profile of levornidazole in the elderly population following the dosing regimens of 500 mg BID and 750 mg once daily for 7 days. Monte Carlo simulation was used for estimating the cumulative fraction of response and probability of target attainment of both dosing regimens against Bacteroides spp. The C max , AUC 0-24, and AUC 0-∞ values of levornidazole in the elderly group were 11.98 μg/mL, 131.36 μg·h/mL, and 173.61 μg·h/mL, respectively. The t 1/2 , CL t , and mean residence time from time 0 to infinity were 12.21 hours, 2.91 L/h, and 16.46 hours. The metabolic ratios of metabolites (M) 1, 2, 4, and 6 were 90% against B fragilis and other Bacteroides spp, and the probability of target attainment was >90% when the minimum inhibitory concentration was ≤1 μg/mL, in both groups. No dosing regimen adjustment is suggested when levornidazole is used in elderly patients with normal hepatic functioning and mild renal dysfunction. The findings from the PK/PD analysis imply that both regimens may achieve satisfactory clinical and microbiological efficacy against anaerobic infections in elderly patients. Chinese Clinical Trial Registry (http://www.chictr.org.cn) identifier: ChiCTR-OPC-16007938. Copyright © 2017 Elsevier HS Journals, Inc. All

  14. Pharmacokinetic Modeling of Voriconazole To Develop an Alternative Dosing Regimen in Children.

    Science.gov (United States)

    Gastine, Silke; Lehrnbecher, Thomas; Müller, Carsten; Farowski, Fedja; Bader, Peter; Ullmann-Moskovits, Judith; Cornely, Oliver A; Groll, Andreas H; Hempel, Georg

    2018-01-01

    The pharmacokinetic variability of voriconazole (VCZ) in immunocompromised children is high, and adequate exposure, particularly in the first days of therapy, is uncertain. A population pharmacokinetic model was developed to explore VCZ exposure in plasma after alternative dosing regimens. Concentration data were obtained from a pediatric phase II study. Nonlinear mixed effects modeling was used to develop the model. Monte Carlo simulations were performed to test an array of three-times-daily (TID) intravenous dosing regimens in children 2 to 12 years of age. A two-compartment model with first-order absorption, nonlinear Michaelis-Menten elimination, and allometric scaling best described the data (maximal kinetic velocity for nonlinear Michaelis-Menten clearance [ V max ] = 51.5 mg/h/70 kg, central volume of distribution [ V 1 ] = 228 liters/70 kg, intercompartmental clearance [ Q ] = 21.9 liters/h/70 kg, peripheral volume of distribution [ V 2 ] = 1,430 liters/70 kg, bioavailability [ F ] = 59.4%, K m = fixed value of 1.15 mg/liter, absorption rate constant = fixed value of 1.19 h -1 ). Interindividual variabilities for V max , V 1 , Q , and F were 63.6%, 45.4%, 67%, and 1.34% on a logit scale, respectively, and residual variability was 37.8% (proportional error) and 0.0049 mg/liter (additive error). Monte Carlo simulations of a regimen of 9 mg/kg of body weight TID simulated for 24, 48, and 72 h followed by 8 mg/kg two times daily (BID) resulted in improved early target attainment relative to that with the currently recommended BID dosing regimen but no increased rate of accumulation thereafter. Pharmacokinetic modeling suggests that intravenous TID dosing at 9 mg/kg per dose for up to 3 days may result in a substantially higher percentage of children 2 to 12 years of age with adequate exposure to VCZ early during treatment. Before implementation of this regimen in patients, however, validation of exposure, safety, and tolerability in a carefully designed

  15. Response of broiler chickens to different dietary crude protein and feeding regimens

    Directory of Open Access Journals (Sweden)

    JO Oyedeji

    2005-09-01

    Full Text Available Five isocaloric (3200kcal/kg diets were used in an experiment designed to investigate the effects of dietary crude protein (CP and feeding regimens on broiler performance. Day-old broilers were randomly distributed into four groups using a completely randomized design. Each group was replicated three times with ten broiler chicks per replicate. The experiment lasted for eight weeks. Broilers in group 1 received 23% CP from 0 to 3 weeks, 20% CP from 3 to 6 weeks and 18% CP from 6 to 8 weeks, while broilers in group 2 received 23% CP between 0 and 6 weeks and 18% CP between 6 and 8 weeks. Besides, broilers in group 3 were fed 23% CP from 0 to 4 weeks and 16% CP from 4 to 8 weeks, whereas group 4 was given 18% CP from 0 to weeks. Water was supplied ad libitum for broilers in the different dietary groups. A metabolic trial was carried out on the third week of the experiment using a total collection method. Proximate analyses of diets and faecal samples were performed according to the methods outlined by the Association Of the Official Analytical Chemists. Results at market age showed that broiler performance with respect to feed intake, weight gain, feed to gain ratio and water intake were not significantly influenced by CP regimens (p>0.05. Furthermore, CP regimens did not significantly influence broilers liveability (p>0.05. Protein retention, fat utilization and available fiber were not significantly influenced among treatments (p> 0.05. Economic data showed that cost to benefit ratio of producing broilers was comparable among broilers for all CP regimens used in this trial (p>0.05. It was concluded that a single diet of 18% CP and 3200kcal/kg metabolizable energy would be most suitable and convenient for farmers who are engaged in on-farm feed production for broilers as compared with the standard feeding regimens of broiler starter and broiler finisher diets.

  16. Evolution of drug resistance in HIV infected patients remaining on a virologically failing cART regimen

    DEFF Research Database (Denmark)

    Cozzi-Lepri, A; Phillips, AN; Ruiz, L

    2007-01-01

    OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points...... to the failing regimen were still receiving benefit from treatment. An overall 6-monthly increase of 1.96 (SD, 2.23) International Aids Society-mutations and an average loss of 1.25 (SD, 1.81) active drugs were estimated. In comparison with patients with GSS_f-t0 = 0, the number of active drugs lost was -1...

  17. Effects of four dim vs high intensity red color light regimens on growth performance and welfare of broilers

    Directory of Open Access Journals (Sweden)

    D. Senaratna

    2018-01-01

    Full Text Available Objective Broilers show clear preference towards red color light (RL. However setting of an optimum light intensity is difficult since dim intensities that favor growth reduce welfare. This experiment was conducted to test the most effective RL intensity regimen (Dim [5 lux; DI] vs high [320 lux; HI] in combination applied at different growth stages that favors for both performance and welfare. Methods Complete randomize design was adopted with 6 replicates. Treatments were; T1 = early DI (8–21 d+latter HI (22–35 d; T2 = early DI (8–28 d+latter HI (29–35 d, T3 = early HI (8–21 d+latter DI (22–35 d, T4 = early HI (8–28 d+latter DI (29–35 d and T5 = control (white light; WT (8–35 d at medium intensity (20 lux. Body weight (BW, weight gain (WG, water/feed intake and ratio, feed conversion ratios (FCR were assessed. Common behaviours (15 were recorded by scan sampling method. Lameness, foot pad dermatitis, breast blisters, hock burning damage were assessed as welfare parameters. Fear reactions were tested using Tonic Immobility Test. Ocular and carcass evaluations were done. Meat and tibiae were analyzed for fat and bone ash respectively. Results On 35 d, the highest BW (2,155.72±176 g, WG (1,967.78±174 g were recorded by T2 compared to WT (BWWT = 1,878.22±155, WGWT = 1,691.83±160. But, application of RL, either DI, or HI during early/latter stage had no significant effect on FCR. Under HI, birds showed much higher active behaviours. DI encourages eating. Though LI changed from DI to HI, same trend could be seen even under HI. The highest leg strength (218.5±120 s was recorded by T2. The lowest leg strength (64.58±33 s and the highest ocular weight (2.48±1 g were recorded by T1. Significantly (p<0.05 the highest skin weight (162.17±6 g but the lowest fat% in meat (13.03%±5% was recorded by T2. Conclusion Early exposure to DI-RL up to 28 days followed by exposure to HI-RL is the most favorable lighting regimen for

  18. Rabeprazole, Minocycline, Amoxicillin, and Bismuth as First-Line and Second-Line Regimens for Helicobacter pylori Eradication.

    Science.gov (United States)

    Song, Zhiqiang; Suo, Baojun; Zhang, Lingyun; Zhou, Liya

    2016-12-01

    Because of general unavailability of tetracycline, common adverse effects, and complicated administration, the clinical application of bismuth quadruple therapy often faces difficulties. Whether the combination of minocycline and amoxicillin can replace tetracycline and metronidazole for Helicobacter pylori eradication remains unclear. This study was to determine the efficacy, compliance, and safety of rabeprazole, minocycline, amoxicillin, and bismuth (RMAB) therapy as first-line and second-line regimens. Between July 2013 and December 2015, a total of 160 patients in first-line and 70 patients in second-line therapies received rabeprazole 10 mg, minocycline 100 mg, amoxicillin 1000 mg, and bismuth potassium citrate 220 mg twice daily for 14 days. Eradication status was assessed 6-12 weeks after treatment. RMAB therapy achieved the eradication rates of 87.5% (95% confidence interval, 81.9-92.5%, intention-to-treat analysis), 90.9% (85.7-95.5%, modified intention-to-treat analysis), and 92.6% (88.5-96.6%, per-protocol analysis) in first-line therapy in a setting with high antibiotic resistance rates (amoxicillin 3.4%, clarithromycin 39.7%, metronidazole 60.3%, levofloxacin 36.2%, tetracycline 3.4%, and minocycline 6.9%). As for second-line therapy, the eradication rates were 82.9% (74.3-91.4%, intention-to-treat analysis), 86.6% (77.6-94.0%, modified intention-to-treat analysis), and 89.1% (81.3-95.3%, per-protocol analysis). Totally, 24.0% patients had adverse effects, 2.2% discontinued medications, and good compliance was achieved in 94.7%. Poor compliance and minocycline resistance were identified as the risk factors for treatment failure. Significant differences in efficacy existed among the groups of both sensitive (48/51 and 18/20), isolated amoxicillin resistance (1/1 and 0/0), isolated minocycline resistance (2/3 and 1/1), and dual resistance (0/1 and 0/1) in both first-line (p = .004) and second-line (p = .035) therapies. The eradication efficacies of RMAB

  19. Advances in combination therapy of lung cancer

    DEFF Research Database (Denmark)

    Wu, Lan; Leng, Donglei; Cun, Dongmei

    2017-01-01

    Lung cancer is a complex disease caused by a multitude of genetic and environmental factors. The progression of lung cancer involves dynamic changes in the genome and a complex network of interactions between cancer cells with multiple, distinct cell types that form tumors. Combination therapy......, including small molecule drugs and biopharmaceuticals, which make the optimization of dosing and administration schedule challenging. This article reviews the recent advances in the design and development of combinations of pharmaceuticals for the treatment of lung cancer. Focus is primarily on rationales...... for the selection of specific combination therapies for lung cancer treatment, and state of the art of delivery technologies and dosage regimens for the combinations, tested in preclinical and clinical trials....

  20. An optimised age-based dosing regimen for single low-dose primaquine for blocking malaria transmission in Cambodia.

    Science.gov (United States)

    Leang, Rithea; Khu, Naw Htee; Mukaka, Mavuto; Debackere, Mark; Tripura, Rupam; Kheang, Soy Ty; Chy, Say; Kak, Neeraj; Buchy, Philippe; Tarantola, Arnaud; Menard, Didier; Roca-Felterer, Arantxa; Fairhurst, Rick M; Kheng, Sim; Muth, Sinoun; Ngak, Song; Dondorp, Arjen M; White, Nicholas J; Taylor, Walter Robert John

    2016-10-27

    In 2012, the World Health Organization recommended the addition of single low-dose primaquine (SLDPQ, 0.25 mg base/kg body weight) to artemisinin combination therapies to block the transmission of Plasmodium falciparum without testing for glucose-6-phosphate dehydrogenase deficiency. The targeted group was non-pregnant patients aged ≥ 1 year (later changed to ≥ 6 months) with acute uncomplicated falciparum malaria, primarily in countries with artemisinin-resistant P. falciparum (ARPf). No dosing regimen was suggested, leaving malaria control programmes and clinicians in limbo. Therefore, we designed a user-friendly, age-based SLDPQ regimen for Cambodia, the country most affected by ARPf. By reviewing primaquine's pharmacology, we defined a therapeutic dose range of 0.15-0.38 mg base/kg (9-22.5 mg in a 60-kg adult) for a therapeutic index of 2.5. Primaquine doses (1-20 mg) were tested using a modelled, anthropometric database of 28,138 Cambodian individuals (22,772 healthy, 4119 with malaria and 1247 with other infections); age distributions were: 0.5-4 years (20.0 %, n = 5640), 5-12 years (9.1 %, n = 2559), 13-17 years (9.1 %, n = 2550), and ≥ 18 years (61.8 %, n = 17,389). Optimal age-dosing groups were selected according to calculated mg base/kg doses and proportions of individuals receiving a therapeutic dose. Four age-dosing bands were defined: (1) 0.5-4 years, (2) 5-9 years, (3) 10-14 years, and (4) ≥15 years to receive 2.5, 5, 7.5, and 15 mg of primaquine base, resulting in therapeutic doses in 97.4 % (5494/5640), 90.5 % (1511/1669), 97.7 % (1473/1508), and 95.7 % (18,489/19,321) of individuals, respectively. Corresponding median (1st-99th centiles) mg base/kg doses of primaquine were (1) 0.23 (0.15-0.38), (2) 0.29 (0.18-0.45), (3) 0.27 (0.15-0.39), and (4) 0.29 (0.20-0.42). This age-based SLDPQ regimen could contribute substantially to malaria elimination and requires urgent evaluation in Cambodia and

  1. Olanzapine-Based Triple Regimens Versus Neurokinin-1 Receptor Antagonist-Based Triple Regimens in Preventing Chemotherapy-Induced Nausea and Vomiting Associated with Highly Emetogenic Chemotherapy: A Network Meta-Analysis.

    Science.gov (United States)

    Zhang, Zhonghan; Zhang, Yaxiong; Chen, Gang; Hong, Shaodong; Yang, Yunpeng; Fang, Wenfeng; Luo, Fan; Chen, Xi; Ma, Yuxiang; Zhao, Yuanyuan; Zhan, Jianhua; Xue, Cong; Hou, Xue; Zhou, Ting; Ma, Shuxiang; Gao, Fangfang; Huang, Yan; Chen, Likun; Zhou, Ningning; Zhao, Hongyun; Zhang, Li

    2018-01-12

    The current antiemetic prophylaxis for patients treated with highly emetogenic chemotherapy (HEC) included the olanzapine-based triplet and neurokinin-1 receptor antagonists (NK-1RAs)-based triplet. However, which one shows better antiemetic effect remained unclear. We systematically reviewed 43 trials, involving 16,609 patients with HEC, which compared the following antiemetics at therapeutic dose range for the treatment of chemotherapy-induced nausea and vomiting: olanzapine, aprepitant, casopitant, fosaprepitant, netupitant, and rolapitant. The main outcomes were the proportion of patients who achieved no nausea, complete response (CR), and drug-related adverse events. A Bayesian network meta-analysis was performed. Olanzapine-based triple regimens showed significantly better no-nausea rate in overall phase and delayed phase than aprepitant-based triplet (odds ratios 3.18, 3.00, respectively), casopitant-based triplet (3.78, 4.12, respectively), fosaprepitant-based triplet (3.08, 4.10, respectively), rolapitant-based triplet (3.45, 3.20, respectively), and conventional duplex regimens (4.66, 4.38, respectively). CRs of olanzapine-based triplet were roughly equal to different NK-1RAs-based triplet but better than the conventional duplet. Moreover, no significant drug-related adverse events were observed in olanzapine-based triple regimens when compared with NK-1RAs-based triple regimens and duplex regimens. Additionally, the costs of olanzapine-based regimens were obviously much lower than the NK-1RA-based regimens. Olanzapine-based triplet stood out in terms of nausea control and drug price but represented no significant difference of CRs in comparison with NK-1RAs-based triplet. Olanzapine-based triple regimens should be an optional antiemetic choice for patients with HEC, especially those suffering from delayed phase nausea. According to the results of this study, olanzapine-based triple antiemetic regimens were superior in both overall and delayed

  2. Progestational effects of combinations of gestodene on the postmenopausal endometrium during hormone replacement therapy.

    Science.gov (United States)

    Byrjalsen, I; Bjarnason, N H; Christiansen, C

    1999-03-01

    The aim of the study was to assess the dose-response effects on the postmenopausal endometrium of 3 sequential combined hormone replacement regimens and 1 continuous combined hormone replacement regimen of estradiol and gestodene. In this 2-year double-blind, placebo-controlled study, 278 healthy postmenopausal women received either 2 mg estradiol sequentially combined with 50 microg or 25 microg gestodene, 1 mg estradiol sequentially or continuously combined with 25 microg gestodene, or placebo. All 4 hormone treatment regimens produced a safe endometrial histologic appearance. The regimens that were based on the lower dose of 1 mg estradiol was associated with less uterine bleeding than were those that were based on 2 mg estradiol. For sequentially opposing the 2 mg dose of estradiol, the dose of 25 microg gestodene was less efficient in producing secretory activity than was the dose of 50 microg gestodene. The measurement of placental protein 14 in serum reflected the secretory transformation of the endometrial buildup. The reduction in bleeding episodes associated with regimens with lower estradiol doses may lead to improved long-term therapy compliance by menopausal women. The potency of progestogens can be assessed by measuring the serum concentration of placental protein 14.

  3. DEVELOPMENT OF AZATHIOPRINE-BASED TREATMENT REGIMEN FOR PATIENTS WITH STEROID RESISTANT PEMPHIGUS BASED ON ASSESSMENT OF MOLECULAR MECHANISMS AT THE POST-RECEPTOR LEVEL

    Directory of Open Access Journals (Sweden)

    O. Yu. Olisova

    2016-01-01

    Full Text Available Background: Autoimmune pemphigus is the most severe skin and mucous membranes disorders with production of IgG autoantibodies to desmogleins 1 and 3. Administration of systemic corticosteroids may help to abrogate active signs of pemphigus. However, some patients do not give an adequate response to systemic glucocorticosteroid monotherapy, as well as to their combination with immune suppressants and cytostatic agents. Aim: To develop an azathioprine-based treatment regimen for patients with autoimmune pemphigus resistant to steroids. Materials and methods: At the first step of development of a treatment regimen for patients with steroid-resistant pemphigus we analyzed retrospectively a clinical database on 23 patients who had been treated from 2000 to 2014 and whose treatment regimen included azathioprine, in addition to systemic glucocorticosteroids. At the second step, from 2013 to 2015, we assessed and treated with the azathioprine-based regimen 24 patients with autoimmune pemphigus, 14  of them being steroid resistant and 10, steroid sensitive (control group. To assess molecular mechanisms of steroid resistance at the post-receptor level (effect of prednisolone on incorporation of ³Н-uridine into lymphocyte mRNA, changes of intracellular levels of nuclear transcription factor NF-κB we used a  real-time polymerase chain reaction, radioisotope method and liquid scintillation radiometry. Results: At the first step, we developed an azathioprine-based treatment regimen for patients with steroid resistant autoimmune pemphigus. Initial dose of azathioprine was 150 mg daily. After achievement of response, the dose was decreased to 100 mg daily. When the dose of systemic glucocorticosteroids was decreased to 20  mg daily, the dose of azathioprine was decreased to 50 mg daily, thereafter steroid resistant patients were taking azathioprine at a dose of 50 mg daily from 3  months to 2.5  years. Investigation of molecular mechanisms

  4. [Efficacy and toxicity of vinorelbine (NVB)-based regimens in patients with metastatic triple negative breast cancer (mTNBC) pretreated with anthracyclines and taxanes].

    Science.gov (United States)

    Du, Feng; Yuan, Peng; Luo, Yang; Wang, Jiayu; Ma, Fei; Cai, Ruigang; Fan, Ying; Li, Qing; Zhang, Pin; Xu, Binghe

    2015-10-01

    To assess the efficacy of vinorelbine (NVB)-based regimens in patients with metastatic triple negative breast cancer (mTNBC) pretreated with anthracyclines and taxanes. Clinical data of 48 patients diagnosed and treated for mTNBC between 2004 and 2012 at the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) were retrospectively analyzed. All patients were pretreated with anthracyclines and at least one taxane in neo-adjuvant, adjuvant or chemotherapy for mTNBC and patients should be having at least one measurable metastatic lesion. Totally, 48 patients were included in this study, of which 21 cases received first-line chemotherapy and 27 cases received second-line chemotherapy. Based on the regimen they received, 22 patients were treated with NVB plus platinum (NP), and 26 patients with NVB plus capecitabine (NX). After 70 months follow-up, in the total group of patients, the objective response rate was 20.8%, clinical benefit rate was 43.8%, median progression free survival (PFS) was 4.4 months and median overall survival (OS) was 15.5 months. In addition, the ORR was significantly better in the NP arm versus NX arm (33.8% vs.7.7%, P=0.029) as well as PFS was statistically improved in the NP arm than NX arm (5.3 m vs. 3.0 m, P=0.023). Similar trend was observed in the OS, although the difference was not statistically significant (27.7 m vs. 14.8 m, P=0.077). In all, the most frequently reported adverse events were G1/2 gastrointestinal toxicity (68.8%) and neutropenia (62.5%) . No significant difference was observed between the NP arm and NX arm (P>0.05). The percentage of patients who delayed chemotherapy administration in the NP arm and NX arm was 9.1% (n=2), and 3.8% (n=1), respectively. NVB-based combination chemotherapy demonstrates moderate efficacy in mTNBC patients pretreated with anthracyclines and one taxane with manageable toxicity. NP regimen shows potential superiority over NX regimen, and should be further verified in randomized phase III

  5. Provider knowledge of treatment policy and dosing regimen with artemether-lumefantrine and quinine in malaria-endemic areas of western Kenya.

    Science.gov (United States)

    Watsierah, Carren A; Onyango, Rosebella O; Ombaka, James H; Abong'o, Benard O; Ouma, Collins

    2012-12-29

    Due to widespread anti-malarial drug resistance in many countries, Kenya included, artemisinin-based Combination Therapy (ACT) has been adopted as the most effective treatment option against malaria. Artemether-lumefantrine (AL) is the first-line ACT for treatment of uncomplicated malaria in Kenya, while quinine is preferred for complicated and severe malaria. Information on the providers' knowledge and practices prior to or during AL and quinine implementation is scanty. The current study evaluated providers' knowledge and practices of treatment policy and dosing regimens with AL and quinine in the public, private and not-for-profit drug outlets. A cross-sectional survey using three-stage sampling of 288 (126 public, 96 private and 66 not-for-profits) providers in drug outlets was conducted in western Kenya in two Plasmodium falciparum-endemic regions with varying malarial risk. Information on provider in-service training, knowledge (qualification, treatment policy, dosing regimen, recently banned anti-malarials) and on practices (request for written prescription, prescription of AL, selling partial packs and advice given to patients after prescription), was collected. Only 15.6% of providers in private outlets had received any in-service training on AL use. All (100%) in public and majority (98.4%) in not-for-profit outlets mentioned AL as first line-treatment drug. Quinine was mentioned as second-line drug by 47.9% in private outlets. A total of 92.0% in public, 57.3% in private and 78.8% in not-for-profit outlets stated correct AL dose for adults. A total of 85.7% of providers in public, 30.2% in private and 41.0% in not-for-profit outlets were aware that SP recommendations changed from treatment for mild malaria to IPTp in high risk areas. In-service training influenced treatment regimen for uncomplicated malaria (P = 0.039 and P = 0.039) and severe malaria (P < 0.0001 and P = 0.002) in children and adults, respectively. Most (82.3%) of private

  6. Systematic Literature Review and Meta-Analysis of Renal Function in Human Immunodeficiency Virus (HIV-Infected Patients Treated with Atazanavir (ATV-Based Regimens.

    Directory of Open Access Journals (Sweden)

    Sandrine Cure

    Full Text Available Some HIV antiretroviral therapies (ART have been associated with renal toxicities, which become of increasing concern as HIV-infected patients age and develop comorbidities. The objective of this study was to evaluate the relative impact of atazanavir (ATV-based regimens on the renal function of adult patients with HIV. We conducted a systematic literature review by searching PubMed, EMBASE, Cochrane library, and the CRD from 2000 until March 2013. Major HIV-related conferences occurring in the past two years were also searched. All randomized clinical trials and large cohort studies assessing renal function in treatment-naïve and/or treatment-experienced HIV patients on ATV-based regimens were included. Fixed-effect mixed-treatment network analyses were carried out on the most frequently reported renal outcomes. 23 studies met the inclusion criteria, and change in estimated glomerular filtration rate (eGFR from baseline to 48 weeks was identified as the main outcome. Two networks including, respectively, six studies (using the Cockcroft-Gault method and four studies (using MDRD and CKD-EPI were analysed. With CG network, ATV/r + TDF/FTC was associated with lower impact on the decline of eGFR than ATV/cobicistat + TDF/FTC but with higher decrease in eGFR than ATV/r + ABC/3TC (difference in mean change from baseline in eGFR respectively +3.67 and -3.89. The use of ATV/cobicistat + TDF/FTC led to a similar decline in eGFR as EVG/cobicistat/TDF/FTC. With respect to third agents combined with TDF/FTC, ATV/r had a lower increase in eGFR in comparison to EFV, and no difference was shown when compared to SQV/r and DRV/r. The effect of ATV-based regimens on renal function at 48 weeks appears similar to other ART regimens and appears to be modest regardless of boosting agent or backbone, although TDF containing backbones consistently leads to greater decline in eGFR.

  7. Provider knowledge of treatment policy and dosing regimen with artemether-lumefantrine and quinine in malaria-endemic areas of western Kenya

    Directory of Open Access Journals (Sweden)

    Watsierah Carren A

    2012-12-01

    Full Text Available Abstract Background Due to widespread anti-malarial drug resistance in many countries, Kenya included, artemisinin-based Combination Therapy (ACT has been adopted as the most effective treatment option against malaria. Artemether-lumefantrine (AL is the first-line ACT for treatment of uncomplicated malaria in Kenya, while quinine is preferred for complicated and severe malaria. Information on the providers’ knowledge and practices prior to or during AL and quinine implementation is scanty. The current study evaluated providers’ knowledge and practices of treatment policy and dosing regimens with AL and quinine in the public, private and not-for-profit drug outlets. Methods A cross-sectional survey using three-stage sampling of 288 (126 public, 96 private and 66 not-for-profits providers in drug outlets was conducted in western Kenya in two Plasmodium falciparum-endemic regions with varying malarial risk. Information on provider in-service training, knowledge (qualification, treatment policy, dosing regimen, recently banned anti-malarials and on practices (request for written prescription, prescription of AL, selling partial packs and advice given to patients after prescription, was collected. Results Only 15.6% of providers in private outlets had received any in-service training on AL use. All (100% in public and majority (98.4% in not-for-profit outlets mentioned AL as first line-treatment drug. Quinine was mentioned as second-line drug by 47.9% in private outlets. A total of 92.0% in public, 57.3% in private and 78.8% in not-for-profit outlets stated correct AL dose for adults. A total of 85.7% of providers in public, 30.2% in private and 41.0% in not-for-profit outlets were aware that SP recommendations changed from treatment for mild malaria to IPTp in high risk areas. In-service training influenced treatment regimen for uncomplicated malaria (P = 0.039 and P = 0.039 and severe malaria (P P = 0.002 in children and adults

  8. Cold Autoimmune Hemolytic Anemia due to High-grade non Hodgkin's B cell Lymphoma with Weak Response to Rituximab and Chemotherapy Regimens.

    Science.gov (United States)

    Nazel Khosroshahi, Behzad; Jafari, Mohammad; Vazini, Hossein; Ahmadi, Alireza; Shams, Keivan; Kholoujini, Mahdi

    2015-07-01

    Autoimmune hemolytic anemia (AIHA) is characterized by shortening of red blood cell (RBC) survival and the presence of autoantibodies directed against autologous RBCs. Approximately 20% of autoimmune hemolytic anemia cases are associated with cold-reactive antibody. About half of patients with AIHA have no underlying associated disease; these cases are termed primary or idiopathic. Secondary cases are associated with underlying diseases or with certain drugs. We report herein a rare case of cold autoimmiune hemolytic anemia due to high-grade non-Hodgkin's lymphoma of B-cell type with weak response to rituximab and chemotherapy regimens. For treatment B cell lymphoma, Due to lack of treatment response, we used chemotherapy regimens including R- CHOP for the first time, and then Hyper CVAD, R- ICE and ESHAP were administered, respectively. For treatment of autoimmune hemolytic anemia, we have used the corticosteroid, rituximab, plasmapheresis and blood transfusion and splenectomy. In spite of all attempts, the patient died of anemia and aggressive lymphoma nine months after diagnosis. To our knowledge, this is a rare report from cold autoimmune hemolytic anemia in combination with high-grade non-Hodgkin's lymphoma of B-cell type that is refractory to conventional therapies.

  9. An open-label study of the effects of a 24-day regimen of gestodene 60 microg/ethinylestradiol 15 microg on endometrial histological findings in healthy women.

    Science.gov (United States)

    Oosterbaan, H P

    1999-11-01

    This open-label, non-comparative study was conducted at a single center to evaluate the effects on the endometrium of a 24-day regimen of a combined oral contraceptive containing gestodene (GTD) 60 microg and ethinylestradiol (EE) 15 microg. Healthy parous women who were > or = 18 years old and had had regular menstrual cycles for the prior 3 months were randomly assigned to one of two groups. Subjects in group A underwent endometrial biopsies during the late luteal phase of the pretreatment cycle and between days 15 and 24 of cycle 6. Subjects in group B had biopsies between days 15 and 24 of cycle 3 and during the late luteal phase of the post-treatment cycle. GTD 60 microg/EE 15 microg was taken for the first 24 days of a 28-day cycle, followed by placebo pills for 4 days, for a total of six cycles. Data from 27 women were included in the analyses. Eleven of the 13 evaluable baseline biopsies were classified as secretory. Three of nine subjects with evaluable biopsies at cycle 3 and four of nine subjects with evaluable biopsies at cycle 6 had an atrophic endometrium. Post-treatment biopsies showed a typical secretory endometrium in seven of 11 subjects with evaluable biopsies. The results of this study show that the 24-day regimen of GTD 60 microg/EE 15 microg produced effective endometrial suppression.

  10. Individual patient data meta-analysis of antiplatelet regimens after noncardioembolic stroke or TIA : Rationale and design

    NARCIS (Netherlands)

    Greving, Jacoba P.; Diener, Hans Christoph; Csiba, László; Hacke, Werner; Kappelle, L. Jaap; Koudstaal, Peter J.; Leys, Didier; Mas, Jean Louis; Sacco, Ralph L.; Sivenius, Juhani; Algra, Ale

    2015-01-01

    Background: The Cerebrovascular Antiplatelet Trialists' Collaborative Group was formed to obtain and analyze individual patient data from the major randomized trials of common antiplatelet regimens after cerebral ischemia. Although the risk of stroke can be reduced by antiplatelet drugs, there

  11. Randomized study comparing two regimens of oral sodium phosphates solution versus low-dose polyethylene glycol and bisacodyl.

    Science.gov (United States)

    Malik, Pramod; Balaban, David H; Thompson, William O; Galt, Deborah J B

    2009-04-01

    Low-volume bowel preparation regimens for colonoscopy are reported to improve patient acceptance and compliance. We sought to compare the bowel cleansing efficacy, tolerability, and acceptability of three low-volume regimens: an oral sodium phosphates solution 45/45 ml (NaP-45/45), a reduced-dose oral sodium phosphates solution 45/30 ml (NaP-45/30), and polyethylene glycol plus bisacodyl (PEG-2L). A total of 121 patients were evaluated (mean age 55.2 +/- 8.9 years). Bowel cleansings rated as excellent and good were significantly different among the groups: NaP-45/45 = 98%, NaP-45/30 = 88%, and PEG-2L = 76% (P phosphates regimens (88, 95, and 73%, respectively; P = 0.019). Better cleansing and willingness to retake the regimen was achieved with the oral sodium phosphates solutions than with polyethylene glycol plus bisacodyl.

  12. Effectiveness of current and future regimens for treating genotype 3 hepatitis C virus infection: a large-scale systematic review

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    Hosnieh Fathi

    2017-11-01

    Full Text Available Abstract Background Six distinct genetic variants (genotypes 1 − 6 of hepatitis C virus (HCV exist globally. Certain genotypes are more prevalent in particular countries or regions than in others but, globally, genotype 3 (GT3 is the second most common. Patients infected with HCV GT1, 2, 4, 5 or 6 recover to a greater extent, as measured by sustained virological response (SVR, following treatment with regimens based on direct-acting antivirals (DAAs than after treatment with older regimens based on pegylated interferon (Peg-IFN. GT3, however, is regarded as being more difficult to treat as it is a relatively aggressive genotype, associated with greater liver damage and cancer risk; some subgroups of patients with GT3 infection are less responsive to current licensed DAA treatments. Newer DAAs have become available or are in development. Methods According to PRISMA guidance, we conducted a systematic review (and descriptive statistical analysis of data in the public domain from relevant clinical trial or observational (real-world study publications within a 5-year period (February 2011 to May 2016 identified by PubMed, Medline In-Process, and Embase searches. This was supplemented with a search of five non-indexed literature sources, comprising annual conferences of the AASLD, APASL, CROI, EASL, and WHO, restricted to a 1-year period (April 2015 to May 2016. Results Of the all-oral regimens, the efficacy (SVR12 ≥ 90% of sofosbuvir plus daclatasvir- and velpatasvir-based regimens in clinical trials supports and reinforces their recommendation by guidelines. Other promising regimens comprise grazoprevir + elbasvir + sofosbuvir, and ombitasvir + paritaprevir/ribavirin + sofosbuvir. Newer regimens incorporating pibrentasvir + glecaprevir or grazoprevir + ruzasvir + MK-3682 (uprifosbuvir, offer all-oral, ribavirin-free SVR12 rates consistently greater than 95%. Observational studies report slightly lower overall SVR rates but reflect

  13. Safe induction of labour with low-dose misoprostol, but less effective than the conventional dinoprostone regimen

    DEFF Research Database (Denmark)

    Petersen, Jesper Friis; Bergholt, Thomas; Løkkegaard, Ellen Christine L

    2013-01-01

    Off-label use of the prostaglandin-E1 analogue misoprostol has become standard practice when inducing labour. In Denmark, a low-dosage misoprostol regimen is common. The regimen consists of one 25 µg application on the first day of induction. The registered prostaglandin-E2 analogue dinoprostone...... is used in 3 and 6 mg doses. This study compared induction procedures with dinoprostone and misoprostol in terms of induction time, foetal outcome and maternal outcome....

  14. An accelerated hypofractionated radiotherapy regimen in patients after organ-sparing surgery for stages I–IIA breast cancer

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    I. A. Gladilina

    2016-01-01

    Full Text Available Objective: to assess the results of accelerated hypofractionated radiotherapy and to comparatively analyze it with the standard radiotherapy in patients with stages I–IIA breast cancer (BC after organ-sparing surgery.Materials and methods. A total of 203 patients with stages I–IIA BC underwent radiotherapy after organ-sparing surgery. A control group of 91 patients received the standard radiotherapy (the single focal dose (SFD was 2 Gy 5 times a week, 25 fractions; the total focal dose (TFD was 50 Gy for 5 weeks. A study group of 112 patients had accelerated hypofractionated radiotherapy (SFD 3 Gy 5 times a week, 13 fractions; TFD 39 Gy for 2.3 weeks.Results. Local recurrences were not detected in any patient after the hypofractionated radiotherapy regimen and were diagnosed in 3.3 % of the patients after the standard regimen. There were no statistically significant differences between the groups in 5-year overall and relapsefree survival rates. Further observation revealed a statistically significant difference in 6-year overall survival rates in the study and control groups: 99.1 and 70.4 %, respectively (p ≤ 0.046. The 6-year relapse-free survival rates in patients who had received the accelerated hypo-fractionated radiotherapy regimen were also significantly higher than in those who had the standard radiotherapy regimen: 97.9 and 71.3 %, respectively (p ≤ 0.043. The rate of post-radiation normal tissue damages after the hypofractionated radiotherapy regimen was significantly lower (15.2 % than that after the standard regimen (27.5 %. Good and excellent cosmetic results of treatment were achieved in most (95.1 % patients and did not differ in their frequency after different radiotherapy regimens.Conclusion. The accelerated hypofractionated radiotherapy regimen showed a high efficiency and a favorable toxicity profile in patients with stages I–IIA BC.

  15. safe induction of labour with low-dose misoprostol, but less effective than the conventional dinoprostone regimen

    DEFF Research Database (Denmark)

    Petersen, Jesper Friis; Bergholt, Thomas; Løkkegaard, Ellen Christine L

    2013-01-01

    Off-label use of the prostaglandin-E1 analogue misoprostol has become standard practice when inducing labour. In Denmark, a low-dosage misoprostol regimen is common. The regimen consists of one 25 µg application on the first day of induction. The registered prostaglandin-E2 analogue dinoprostone...... is used in 3 and 6 mg doses. This study compared induction procedures with dinoprostone and misoprostol in terms of induction time, foetal outcome and maternal outcome....

  16. Twice-Daily versus Once-Daily Pramipexole Extended Release Dosage Regimens in Parkinson’s Disease

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    Ji Young Yun

    2017-01-01

    Full Text Available This open-label study aimed to compare once-daily and twice-daily pramipexole extended release (PER treatment in Parkinson’s disease (PD. PD patients on dopamine agonist therapy, but with unsatisfactory control, were enrolled. Existing agonist doses were switched into equivalent PER doses. Subjects were consecutively enrolled into either once-daily-first or twice-daily-first groups and received the prescribed amount in one or two, respectively, daily doses for 8 weeks. For the second period, subjects switched regimens in a crossover manner. The forty-four patients completed a questionnaire requesting preference during their last visit. We measured the UPDRS-III, Hoehn and Yahr stages (H&Y in medication-on state, Parkinson’s disease sleep scale (PDSS, and Epworth Sleepiness Scale. Eighteen patients preferred a twice-daily regimen, 12 preferred a once-daily regimen, and 14 had no preference. After the trial, 14 subjects wanted to be on a once-daily regimen, 25 chose a twice-daily regimen, and 5 wanted to maintain the prestudy regimen. Main reasons for choosing the twice-daily regimen were decreased off-duration, more tolerable off-symptoms, and psychological stability. The mean UPDRS-III, H&Y, and PDSS were not different. Daytime sleepiness was significantly high in the once-daily regimen, whereas nocturnal hallucinations were more common in the twice-daily. Multiple dosing should be considered if once-daily dosing is unsatisfactory. This study is registered as NCT01515774 at ClinicalTrials.gov.

  17. Alternation of antiretroviral drug regimens for HIV infection. Efficacy, safety and tolerability at week 96 of the Swatch Study.

    Science.gov (United States)

    Negredo, Eugenia; Paredes, Roger; Peraire, Joaquim; Pedrol, Enric; Côté, Helene; Gel, Silvia; Fumoz, Carmina R; Ruiz, Lidia; Abril, Vicente; Rodriguez de Castro, Eduardo; Ochoa, Claudia; Martinez-Picado, Javier; Montaner, Julio; Rey-Joly, Celestino; Clotet, Bonaventura

    2004-12-01

    Alternation of antiretroviral drug regimens has been proposed as a novel treatment strategy for HIV infection. However, some concerns persist regarding antiviral efficacy, adherence, toxicity and resistance evolution in the long term. A total of 161 antiretroviral-naive HIV-1-infected patients were randomized to receive stavudine/didanosine/efavirenz (group A) or zidovudine/lamivudine/ nelfinavir (group B) or to alternate between the two regimens every 3 months starting with regimen A (group C). Antiviral efficacy, adherence, safety and tolerability were analysed every 12 weeks. After 96 weeks, time to virological failure was significantly delayed in the alternating regimen compared with the standards of care regimens. Virological suppression was seen in 46%, 48% and 58% of patients in groups A, B and C, respectively, in the intention-to-treat analysis and in 75%, 76% and 97% in the on-treatment analysis (A vs C: P=0.014; B vs C: P=0.016; A vs B: P=0.849). At the end of the study, 94% of patients in group A and 92% in groups B and C reported an adherence greater than 95%. Alternating therapy was associated with a similar impact on CD4+ counts in comparison with the standards of care regimens, as well as a lower mitochondrial DNA/nuclear DNA (mtDNA/nDNA) ratio decrease in the mitochondrial substudy performed on 37 patients. The frequency and intensity of adverse events in the alternating group decreased during subsequent cycles. Our results favour the hypothesis that proactive therapy switching may delay the accumulation of resistance mutations. Moreover, the alternating regimen was well tolerated and adherence remained comparably high in all treatment groups. The lower mtDNA/nDNA ratio decrease observed in this group may imply a lower impact on mitochondrial toxicity than in standard regimens.

  18. Combination contraceptives: effects on weight.

    Science.gov (United States)

    Gallo, Maria F; Lopez, Laureen M; Grimes, David A; Carayon, Florence; Schulz, Kenneth F; Helmerhorst, Frans M

    2014-01-29

    Weight gain is often considered a side effect of combination hormonal contraceptives, and many women and clinicians believe that an association exists. Concern about weight gain can limit the use of this highly effective method of contraception by deterring the initiation of its use and causing early discontinuation among users. However, a causal relationship between combination contraceptives and weight gain has not been established. The aim of the review was to evaluate the potential association between combination contraceptive use and changes in weight. In November 2013, we searched the computerized databases CENTRAL (The Cochrane Library), MEDLINE, POPLINE, EMBASE, and LILACS for studies of combination contraceptives, as well as ClinicalTrials.gov and International Clinical Trials Registry Platform (ICTRP). For the initial review, we also wrote to known investigators and manufacturers to request information about other published or unpublished trials not discovered in our search. All English-language, randomized controlled trials were eligible if they had at least three treatment cycles and compared a combination contraceptive to a placebo or to a combination contraceptive that differed in drug, dosage, regimen, or study length. All titles and abstracts located in the literature searches were assessed. Data were entered and analyzed with RevMan. A second author verified the data entered. For continuous data, we calculated the mean difference and 95% confidence interval (CI) for the mean change in weight between baseline and post-treatment measurements using a fixed-effect model. For categorical data, such as the proportion of women who gained or lost more than a specified amount of weight, the Peto odds ratio with 95% CI was calculated. We found 49 trials that met our inclusion criteria. The trials included 85 weight change comparisons for 52 distinct contraceptive pairs (or placebos). The four trials with a placebo or no intervention group did not find

  19. COMPARISON OF EFFICACY AND FETOMATERNAL OUTCOME WITH LOW DOSE AND STANDARD PRITCHARD’S REGIMEN OF MAGNESIUM SULPHATE IN ECLAMPSIA

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    Nirmala Chamakuri

    2017-11-01

    Full Text Available BACKGROUND Eclampsia, a hypertensive disorder of pregnancy is a common obstetric emergency, which leads to significant maternal morbidity, perinatal morbidity and mortality. The Pritchard’s regimen of magnesium sulphate remains as the standard regimen worldwide. The aim of this study is to compare the effectiveness, side effects and fetomaternal outcome using low-dose magnesium sulphate with the results of Pritchard regime. MATERIALS AND METHODS A comparative prospective study including 120 eclampsia patients designed into group I and group II treated with low-dose magnesium sulphate and Pritchard’s regimen was conducted in the Department of Obstetrics and Gynaecology for a period of 18 months between January 2015 to June 2016. RESULTS In the present study, there was 100% control of seizures in both the groups. No recurrence of seizures were seen in 57 (95% of cases in group II (low-dose regimen and 3 (5% cases showed recurrence, which were controlled by giving additional doses. In group II, loss of patellar reflexes was seen in 6 (10%, reduced urine output was seen in 3 (5% of cases, mild PPH was observed in 3 (5% cases and perinatal mortality in 18 (30% cases, which were lower than that of group I (Pritchard’s regimen. CONCLUSION Low-dose magnesium sulphate is effective in controlling convulsions in eclampsia. This regimen is highly suitable for use in Indian women who are known to have low body mass index

  20. Serum lipid profiles among patients initiating ritonavir-boosted atazanavir versus efavirenz-based regimens

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    Tasker Sybil

    2009-06-01

    Full Text Available Abstract Background Antiretrovirals used to treat HIV-infected patients have the potential to adversely affect serum lipid profiles and increase the risk of cardiovascular disease which is an emerging concern among HIV-infected patients. Since boosted atazanavir and efavirenz are both considered preferred antiretrovirals a head to head comparison of their effects on serum lipids is needed. Aim The primary objective of the study was to compare the effects of atazanavir (boosted and unboosted and efavirenz based regimens on serum lipid profiles. Study Design Prospective cohort study nested within three ongoing cohorts of HIV-infected individuals. Study Population and Methods Participants initiating either atazanavir or efavirenz based regimens with documented pre- and post-initiation lipid values. Multivariate linear regression was conducted to estimate adjusted mean differences between treatment groups for high density lipoprotein cholesterol (HDL-c, non-HDL-c, and log total cholesterol (TC to HDL-c ratio outcomes; log-linear regression models were used to estimate differences in prevalence of low HDL-c and desirable TC. Results The final study population was comprised of 380 efavirenz and 281 atazanavir initiators. Both atazanavir and efavirenz users had increases in serum HDL-c and decreases in TC/HDL ratio. In comparison to individuals initiating efavirenz, boosted atazanavir users on average had lower HDL-c (-4.12 mg/dl, p Conclusion Both efavirenz and atazanavir-based regimens (boosted and unboosted resulted in similar beneficial declines in the TC/HDL ratio.

  1. EXPERIMENTAL CONFIRMATION FOR SELECTION OF IRRADIATION REGIMENS FOR INTRAPERITONEAL PHOTODYNAMIC THERAPY WITH PORPHYRIN AND PHTHALOCYANINE PHOTOSENSITIZERS

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    A. A. Pankratov

    2017-01-01

    Full Text Available Optimized irradiation regimens for intraperitoneal photodynamic therapy with porphyrin and phthalocyanine photosensitizers are determined in in vitro and in vivo studies.The experimental  study on НЕр2 cell line showed that reduce of power density for constant  light dose increased significantly the efficacy of photodynamic therapy (the reduce of power density from 20-80 mW/cm2 to 10 mW/cm2 had the same results (90% cell death for half as much concentration of the photosensitizer.The obtained results were confirmed in vivo in mice with grafted tumor S-37. For light dose of 90 J/cm2  and power density of 25 mW/cm2 none of animals in the experimental  group had total resorption of the tumor. For the same light dose and decrease  of power density to 12 mW/cm2  total tumor resorption was achieved in 34% of animals, 66% of animals died from phototoxic  shock. For twofold decrease  of light dose – to 45 J/cm2  with the same low-intensity power density (12 mW/cm2 we managed total tumor resorption in 100% of animals.In the following studies of optimized irradiation regimen for intrapleural photodynamic therapy the reaction of intact peritoneum of rats on photodynamic exposure was assessed and optimized parameters of laser irradiation, which did not cause necrosis and intense inflammatory reaction of peritoneum, were determined – light dose of 10 J/cm2  with power density of mW/cm2.Thus, the reasonability for use of low-intensity regimens of irradiation for intraperitoneal photodynamic therapy was confirmed experimentally with possibility of high efficacy of treatment without inflammatory reactions of peritoneum.

  2. Outcomes of autologous transplantation for multiple myeloma according to different induction regimens

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    Edvan de Queiroz Crusoe

    2014-01-01

    Full Text Available Background: Induction therapy followed by high-dose chemotherapy and autologous transplantation is the standard treatment for suitable patients with multiple myeloma. Objective: The aim of this study was to assess whether induction therapy with thalidomidecontaining regimens was associated with improved results compared to vincristine, doxorubicin, and dexamethasone, and whether cyclophosphamide, thalidomide, and dexamethasone were associated with better results than thalidomide and dexamethasone. Methods: The records of 152 patients who underwent autologous transplantation at this institution from August of 2004 to January of 2012 were reviewed, selecting those with at least partial response to a maximum of eight cycles of induction therapy and sufficient follow-up information for analysis. Results: This study included 89 patients; 44 were female, with a mean age of 55 years (there was a significant trend for increasing age over the years of the study.The median number of induction therapy cycles was four, again with a trend of increase over the years.At least a very good partial response to induction therapy was achieved more often in the cyclophosphamide, thalidomide, and dexamethasone group (61.1% and in the thalidomide and dexamethasone group (59.2% than in the vincristine, doxorubicin, and dexamethasone group (16.2%. The overall median progression-free survival was 34 months, with no statistically significant difference between the three groups. The overall median survival was not reached, and there was no significant difference between the three groups; the estimated five-year overall survival was 55%. Conclusion: Although the quality of responses appeared to be better with thalidomidecontaining regimens, these improvements did not translate into improved long-term outcomes. Given its track record, cyclophosphamide, thalidomide, and dexamethasone is currently considered the preferred regimen for first-line induction therapy in the

  3. Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Van Beneden, Katrien, E-mail: kvbenede@vub.ac.be [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Geers, Caroline [Department of Pathology, Universitair Ziekenhuis Brussel, Brussels (Belgium); Pauwels, Marina [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Mannaerts, Inge [Department of Cell Biology, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Wissing, Karl M. [Department of Nephrology, Universitair Ziekenhuis Brussel, Brussels (Belgium); Van den Branden, Christiane [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Grunsven, Leo A. van, E-mail: lvgrunsv@vub.ac.be [Department of Cell Biology, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium)

    2013-09-01

    Histone deacetylase (HDAC) inhibitors are promising new compounds for the therapy of fibrotic diseases. In this study we compared the effect of two HDAC inhibitors, trichostatin A and valproic acid, in an experimental model of kidney fibrosis. In mice, doxorubicin (adriamycin) can cause nephropathy characterized by chronic proteinuria, glomerular damage and interstitial inflammation and fibrosis, as seen in human focal segmental glomerulosclerosis. Two treatment regimens were applied, treatment was either started prior to the doxorubicin insult or delayed until a significant degree of proteinuria and fibrosis was present. Pre-treatment of trichostatin A significantly hampered glomerulosclerosis and tubulointerstitial fibrosis, as did the pre-treatment with valproic acid. In contrast, the development of proteinuria was only completely inhibited in the pre-treated valproic acid group, and not in the pre-treated trichostatin A animals. In the postponed treatment with valproic acid, a complete resolution of established doxorubicin-induced proteinuria was achieved within three days, whereas trichostatin A could not correct proteinuria in such a treatment regimen. However, both postponed regimens have comparable efficacy in maintaining the kidney fibrosis to the level reached at the start of the treatments. Moreover, not only the process of fibrosis, but also renal inflammation was attenuated by both HDAC inhibitors. Our data confirm a role for HDACs in renal fibrogenesis and point towards a therapeutic potential for HDAC inhibitors. The effect on renal disease progression and manifestation can however be different for individual HDAC inhibitors. - Highlights: • Valproic acid is a potent antiproteinuric drug, whereas trichostatin A is not. • Trichostatin A and valproic acid reduce kidney fibrosis in doxorubicin nephropathy. • Both valproic acid and trichostatin A attenuate renal inflammation.

  4. A low-dose regimen of cisplatin before high-dose cisplatin potentiates ototoxicity.

    Science.gov (United States)

    Harrison, Ryan T; DeBacker, J Riley; Bielefeld, Eric C

    2015-02-01

    Cochlear preconditioning with low doses of kanamycin or noise can reduce susceptibility to noise- and ototoxic drug-induced hearing loss. The current study was undertaken to investigate whether a preconditioning regimen of low-dose cisplatin would alter susceptibility to ototoxicity induced by a single large dose of cisplatin. In vivo study using an animal model. Twenty-six Fischer 344/NHsd rats were used in the study. The low-dose regimen consisted of cisplatin (2 or 3 mg/kg) given every 2 weeks by intraperitoneal injection. Control animals received injections of saline on the same schedule as the cisplatin injections. Four injections were done in total. Following the preconditioning interval, seven of the animals were sacrificed for hair cell analyses. The remaining 19 animals were exposed to 12 mg/kg cisplatin by intraperitoneal infusion to induce cochlear injury. Auditory brainstem response (ABR) thresholds were measured 3 days after cisplatin, and the cochleae from the 19 animals were harvested and analyzed. Statistical analyses revealed no threshold shifts, but mild outer hair cell losses, after the low-dose regimen. ABR threshold shifts in the rats exposed to the 12 mg/kg cisplatin dose were significantly higher at day 3 in the animals that underwent preconditioning with low-dose cisplatin. Outer hair cell losses were also greater in the preconditioned animals. Preconditioning with low-dose cisplatin, using the protocol applied in the current experiment, created potentiation of cisplatin ototoxicity, rather than protection from it. There are numerous possible explanations for this effect that should be considered. NA. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  5. HAG regimen improves survival in adult patients with hypocellular acute myeloid leukemia.

    Science.gov (United States)

    Hu, Xiaoxia; Fu, Weijun; Wang, Libing; Gao, Lei; Lü, Shuqin; Xi, Hao; Qiu, Huiying; Chen, Li; Chen, Jie; Ni, Xiong; Xu, Xiaoqian; Zhang, Weiping; Yang, Jianmin; Wang, Jianmin; Song, Xianmin

    2016-01-19

    Hypocellular acute myeloid leukemia (Hypo-AML) is a rare disease entity. Studies investigating the biological characteristics of hypo-AML have been largely lacking. We examined the clinical and biological characteristics, as well as treatment outcomes of hypo-AML in our institutes over a seven years period. We retrospectively analyzed data on 631 adult AML patients diagnosed according to the French-American-British (FAB) classification and WHO classification of tumors of haematopoietic and lymphoid tissue, including 43 patients with hypo-AML. Biological variables, treatment outcomes and follow-up data on hypo-AML patients were analyzed. Out of 631 AML patients, 47 (7.4%) were diagnosed as hypo-AML, out of which 43 patients were evaluable. Compared with non-hypocellular AML, hypo-AML patients tended to be older (P = 0.05), more likely to present with leukocytopenia (P < 0.01) and anterior hematological diseases (P = 0.02). The overall complete remission (CR) rate, disease free survival (DFS), and overall survival (OS) in hypo-AML patients were comparable to those in non-hypo AML patients. Twenty-seven (62.8%) patients with hypocellular AML were treated with the standard regimen of anthracyclines and cytarabine (XA) (associated CR rate: 51.9%; median OS: 7 months; median DFS: 6.5 months). Sixteen (37.2%) patients were treated with a priming regimen containing homoharringtonine, cytarabine and G-CSF (HAG) (associated CR rate: 81.25%; median OS: 16 months; median DFS: 16 months). The overall prognosis of hypo-AML was not inferior to that of non-hypo AML. HAG regimen might increase response rates and improve survival in hypo-AML patients.

  6. Efficacy of neo-adjuvant chemotherapy with TEC regimen on breast cancer.

    Science.gov (United States)

    Gu, Xi; Zhang, Yang; Chen, Long; Guo, Jiao; Zhang, Wen-Hai

    2015-02-01

    This study aims to investigate the efficacy of neo-adjuvant chemotherapy with TEC regimen (taxotere-epirubicin-cyclophosphamide) in the treatment of breast cancer (BC) patients. Total of 118 BC patients were recruited from the Department of Breast Surgery in Shengjing Hospital of China Medical University from January 1, 2010 to December 31, 2012, in this study. The clinical data and serum samples were collected from each patient prior to the study. All patients were given four cycles of TEC chemotherapy before surgery. The overall response rate of TEC regimen in the treatment of BC was 67.8% (80/118), clinical complete response rate was 3.4% (4/118), and clinical partial response rate was 64.4% (76/118). Furthermore, we found that age, tumor size, lymph node metastasis and clinical stages of patients had no statistically significant difference (all P > 0.05). Both negative ER status and negative PR status were statistically related to better response (P = 0.033 and P = 0.024, respectively) when compared with the positive ER status and positive PR status, while such association was not observed between the negative HER-2 status and positive HER-2 status (P > 0.05). In addition, the efficacy of triple-negative breast cancer was significantly better than that of luminal A, luminal B and HER-2+ cancers (all P 0.05). Our study support the view that BC cases under the TEC chemotherapy were related to higher overall response rates; and the chemotherapy with the TEC regimen could be served as an effective therapy in the treatment of BC.

  7. A novel approach to pharmacodynamic assessment of antimicrobial agents: new insights to dosing regimen design.

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    Vincent H Tam

    Full Text Available Pharmacodynamic modeling has been increasingly used as a decision support tool to guide dosing regimen selection, both in the drug development and clinical settings. Killing by antimicrobial agents has been traditionally classified categorically as concentration-dependent (which would favor less fractionating regimens or time-dependent (for which more frequent dosing is preferred. While intuitive and useful to explain empiric data, a more informative approach is necessary to provide a robust assessment of pharmacodynamic profiles in situations other than the extremes of the spectrum (e.g., agents which exhibit partial concentration-dependent killing. A quantitative approach to describe the interaction of an antimicrobial agent and a pathogen is proposed to fill this unmet need. A hypothetic antimicrobial agent with linear pharmacokinetics is used for illustrative purposes. A non-linear functional form (sigmoid Emax of killing consisted of 3 parameters is used. Using different parameter values in conjunction with the relative growth rate of the pathogen and antimicrobial agent concentration ranges, various conventional pharmacodynamic surrogate indices (e.g., AUC/MIC, Cmax/MIC, %T>MIC could be satisfactorily linked to outcomes. In addition, the dosing intensity represented by the average kill rate of a dosing regimen can be derived, which could be used for quantitative comparison. The relevance of our approach is further supported by experimental data from our previous investigations using a variety of gram-negative bacteria and antimicrobial agents (moxifloxacin, levofloxacin, gentamicin, amikacin and meropenem. The pharmacodynamic profiles of a wide range of antimicrobial agents can be assessed by a more flexible computational tool to support dosing selection.

  8. Increased risk of breast cancer following different regimens of hormone replacement therapy frequently used in Europe

    DEFF Research Database (Denmark)

    Stahlberg, Claudia; Pedersen, Anette Tønnes; Lynge, Elsebeth

    2004-01-01

    Epidemiologic studies have shown an increased risk of breast cancer following hormone replacement therapy (HRT). The aim of this study was to investigate whether different treatment regimens or the androgenecity of progestins influence the risk of breast cancer differently. The Danish Nurse Cohort...... were ascertained using nationwide registries. The follow-up ended on 31 December 1999. Women with former cancer diagnoses, women with missing information on HRT, surgical menopause, premenopausal, as well as hysterectomized women were excluded, leaving 10,874 for analyses. Statistical analyses were...

  9. Influence of drug load and physical form of cinnarizine in new SNEDDS dosing regimens

    DEFF Research Database (Denmark)

    Siqueira, Scheyla D V S; Müllertz, Anette; Gräeser, Kirsten

    2017-01-01

    , compared to the aqueous suspension. Since the drug level in the aqueous phase is traditionally considered as the fraction available for absorption, a lack of in vitro-in vivo relation was observed. This study revealed that the physical form of CIN in the current SNEDDS does not affect CIN absorption......The aim of this work was to evaluate the influence of drug load and physical form of cinnarizine (CIN) in self-nanoemulsifying drug delivery systems (SNEDDS) on absorption in rats. Further, the predictivity of the dynamic in vitro lipolysis model was evaluated. The following dosing regimens were...

  10. A comparison of patient pain responses and medication regimens after hip/knee replacement.

    Science.gov (United States)

    Smith-Miller, Cheryl A; Harlos, Linda; Roszell, Sheila Serr; Bechtel, Gregory A

    2009-01-01

    Increased emphasis on adequate pain control as a patient expectation and a change in professional practice standards has prompted research on new mechanisms of pain medication delivery in an effort to improve outcomes and efficacy. The purpose of this study was to compare pain scores of patients receiving extended release epidural morphine (EREM) with those receiving traditional pain control regimens. Retrospective chart reviews were performed on all patients who had had first-time, elective, nontraumatic, unilateral hip or knee replacement from January to June 2006. All patients received either intraoperative EREM or a traditional pain control regimen. Medication regimens were coded and noted at patients' arrival on the unit (baseline), at 16 hr, and at 48 hr postoperatively. The sample consisted of surgical patients (N = 65) having first-time, nontraumatic hip/knee surgery. Of the sample, 39% (n = 25) were men and 61% (n = 40) were women, with a mean age of 65.25 years (SD = 15.28). Knee replacement surgery was the most frequent surgery at 57% (n = 36), with women representing 75% (n = 28) of the total knee surgical procedures. Hip surgical procedures were equally divided between men (n =11) and women (n = 11). Postoperative pain was assessed within 1 hr of admission to the unit for 98.5% (n = 64) of patients and reassessed at 15-17 hr for 90.8% (n = 59) of the sample, suggesting that the assessment and documentation of patient pain level were a high priority for the nurses. Pain scores were not correlated with age during the 3 time points in the study. Women reported a significantly higher level of pain upon admission to the unit than men, t(62) = 2.697, p Pain scores for both groups were relatively low with an average score of 3.1 at the time of postoperative admission decreasing to an average of 2.7 at 16 and 24 hours. There were no significant differences in patients reported pain levels between the EREM and traditional control regimens.

  11. Severe Dopaminergic Neurotoxicity in Primates After a Common Recreational Dose Regimen of MDMA (``Ecstasy'')

    Science.gov (United States)

    Ricaurte, George A.; Yuan, Jie; Hatzidimitriou, George; Cord, Branden J.; McCann, Una D.

    2002-09-01

    The prevailing view is that the popular recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, or ``ecstasy'') is a selective serotonin neurotoxin in animals and possibly in humans. Nonhuman primates exposed to several sequential doses of MDMA, a regimen modeled after one used by humans, developed severe brain dopaminergic neurotoxicity, in addition to less pronounced serotonergic neurotoxicity. MDMA neurotoxicity was associated with increased vulnerability to motor dysfunction secondary to dopamine depletion. These results have implications for mechanisms of MDMA neurotoxicity and suggest that recreational MDMA users may unwittingly be putting themselves at risk, either as young adults or later in life, for developing neuropsychiatric disorders related to brain dopamine and/or serotonin deficiency.

  12. Gemcitabine and oxaliplatinum: an effective regimen in patients with refractory and relapsing Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    Gutierrez A

    2014-11-01

    Full Text Available Antonio Gutierrez,1,* Jose Rodriguez,1,* Jordi Martinez-Serra,1 Jordi Gines,2 Pilar Paredes,1 Florencia Garcia,3 Javier Vercher,4 Josep Balanzat,4 Raquel del Campo,5 Pilar Galan,6 Miguel Morey,1 Antonia Sampol,1,7 Andres Novo,1 Leyre Bento,1 Lucia García,1 Joan Bargay,5 Joan Besalduch1,7 1Service of Hematology, 2Service of Pharmacy, 3Service of Oncology, Son Espases University Hospital, Palma de Mallorca, Spain; 4Service of Hematology, Can Misses Hospital, Ibiza, Spain; 5Service of Hematology, Son Llatzer Hospital, Palma, Spain; 6Service of Hematology, Mateu Orfila Hospital, Menorca, Spain; 7Service of Hematology, Policlínica Miramar, Instituto de Investigación Sanitaria de Palma (IdISPa, Palma, Spain  *These authors contributed equally to this work Background: Most Hodgkin lymphomas (HL can be cured with current strategies. However, one-third of the cases do not respond or relapse and need salvage regimens. We report the results of a retrospective study using the gemcitabine and oxaliplatinum (GemOx regimen.Methods: Patients who relapsed or failed to achieve complete response were eligible and received GemOx salvage therapy. To avoid selection bias and thus to overcome the retrospective nature of the study, all treated patients were included from the pharmacy database.Results: Between 2003–2013, 24 HL patients – relapsing (number [n]=12 or refractory (n=12 – were included, receiving a total of 26 induction treatments with GemOx. Mean previous regimens were 2.38 (42% relapsing after autologous transplantation. Median follow-up was 37 months, and 71% responded (38% of patients achieved complete response. The factors related to better progression-free survival were: B symptoms; response to GemOx; and consolidation with stem cell transplantation. Grades 1 and 2 neurological toxicity was present in 17% of patients. Hematological toxicity was common, with grades 3 and 4 neutropenia (25% and thrombocytopenia (34% observed. Progression

  13. Alternative donor hematopoietic stem cell transplantation for mature lymphoid malignancies after reduced-intensity conditioning regimen

    DEFF Research Database (Denmark)

    Rodrigues, Celso Arrais; Rocha, Vanderson; Dreger, Peter

    2014-01-01

    an allogeneic unrelated donor transplant using umbilical cord blood (n=104) or mobilized peripheral blood stem cells (n=541) after a reduced-intensity conditioning regimen. Unrelated cord blood recipients had more refractory disease. Median follow-up time was 30 months. Neutrophil engraftment (81% vs. 97...... sources except for a higher risk of neutrophil engraftment (hazard ratio=2.12; Pumbilical cord blood...... and matched unrelated donor transplant. Umbilical cord blood is a valuable alternative for patients with lymphoid malignancies lacking an HLA-matched donor, being associated with lower risk of chronic graft-versus-host disease....

  14. Biohydrogenation of Fatty Acids Is Dependent on Plant Species and Feeding Regimen of Dairy Cows

    DEFF Research Database (Denmark)

    Petersen, Majbritt Bonefeld; Jensen, Søren Krogh

    2014-01-01

    and LA between single plant species and feeding regimens. Rumen fluid was collected from cows fed either total mixed ration (TMR), species-rich silage (HERB), or grass silage (GRASS). Five single species (alfalfa, birdsfoot trefoil, chicory, English plantain, and salad burnet) and a grass–clover mixture...... (white clover and ryegrass) were incubated in three replicas up to 30 h and subsequently analyzed for fatty acid content. Michaelis–Menten kinetics was applied for quantifying the BH rate. BH proceeded at the lowest rate in alfalfa and salad burnet (P

  15. Combining writing block treatments: theory and research.

    Science.gov (United States)

    Boice, R

    1992-03-01

    Four traditional formats of treatment for writing blocks (automaticity, regimen, self-control, and social skills training) proved insufficient to maintain unblocking in professorial writers for periods of an academic year. A combined application of the four historically prominent interventions was clearly more effective in terms of stable productivity, manuscripts finished and submitted, and manuscripts accepted for publication. Because writing blocks are too often conceptualized and treated by way of lore, a theory of blocking is proposed that clarifies the fundamental steps in effecting lasting unblocking.

  16. Combined radiochemotherapy of head and neck cancer

    International Nuclear Information System (INIS)

    Schlappack, O.; Springer, B.; Hainz, A.

    1994-01-01

    Advanced tumors of the head and neck are often treated with combined radiochemotherapy. The chemotherapeutic agents used should be active in this tumor type and its adverse effects should not overlap with those of the radiation treatment. Published studies were reviewed and discussed on the basis of these principles. Initially, single agents such as 5-fluorouracil (5-FU) and methotrexate were used in combination with radiotherapy. These combinations caused an improved local tumor control but also an increased mucosal reaction. For mitomycin C it has been shown in a randomized trial that local tumor control was improved without concomitant increased normal tissue toxicity. Also cisplatin and carboplatin were studied in combination with radiotherapy. Unfortunately, there are no results of randomized studies available but these agents do not seem to increase mucosal toxicity. The standard chemotherapy of squamous cell carcinomas of the head and neck is cisplatin and 5-FU. Many studies have been conducted with this chemotherapy in combination with radiotherapy. To this day it has not been shown that the results of an effective radiation treatment or an effective chemotherapy can be improved by these experiments. The explanation for that is that either the chemotherapy or the radiotherapy cannot be given at full dose because the regimen would become too toxic. 5-FU containing polychemotherapy regimens should not be combined with radiation any more because it is known that 5-FU increases the mucosal reaction. Agents that could be studied in the future either alone or in combination with cisplatin or carboplatin are etoposide and taxol. (orig.) [de

  17. Efficacy and safety of weight-based insulin glargine dose titration regimen compared with glucose level- and current dose-based regimens in hospitalized patients with type 2 diabetes: a randomized, controlled study.

    Science.gov (United States)

    Li, Xiaowei; Du, Tao; Li, Wangen; Zhang, Tong; Liu, Haiyan; Xiong, Yifeng

    2014-09-01

    Insulin glargine is widely used as basal insulin. However, published dose titration regimens for insulin glargine are complex. This study aimed to compare the efficacy and safety profile of a user-friendly, weight-based insulin glargine dose titration regimen with 2 published regimens. A total of 160 hospitalized patients with hyperglycemia in 3 medical centers were screened. Our inclusion criteria included age 18 to 80 years and being conscious. Exclusion criteria included pregnancy or breast-feeding and hepatic or renal dysfunction. A total of 149 patients were randomly assigned to receive weight-based, glucose level-based, or dose-based insulin glargine dose titration regimen between January 2011 and February 2013. The initial dose of insulin glargine was 0.2 U/kg. In the weight-based regimen (n = 49), the dose was titrated by increments of 0.1 U/kg daily. In the glucose level-based regimen (n = 51), the dose was titrated by 2, 4, 6, or 8 U daily when fasting blood glucose (FBG) was, respectively, between 7.0 and 7.9, 8.0 and 8.9, 9.0 and 9.9, or ≥10 mmol/L. In the current dose-based regimen (n = 49), titration was by daily increments of 20% of the current dose. The target FBG in all groups was ≤7.0 mmol/L. The incidence of hypoglycemia was recorded. One-way ANOVA and χ(2) test were used to compare data between the 3 groups. All but 1 patient who required additional oral antidiabetic medication completed the study. The mean (SD) time to achieve target FBG was 3.2 (1.2) days with the weight-based regimen and 3.7 (1.5) days with the glucose level-based regimen (P = 0.266). These times were both shorter than that achieved with the current dose-based regimen (4.8 [2.8] days; P = 0.0001 and P = 0.005, respectively). The daily doses of insulin glargine at the study end point were 0.43 (0.13) U/kg with the weight-based regimen, 0.50 (0.20) U/kg with the glucose level-based regimen, and 0.47 (0.23) U/kg with the current dose-based regimen (P = 0.184). The incidence

  18. Population pharmacokinetic and pharmacodynamic analysis to support treatment optimization of combination chemotherapy with indisulam and carboplatin.

    Science.gov (United States)

    Zandvliet, Anthe S; Schellens, Jan H M; Dittrich, Christian; Wanders, Jantien; Beijnen, Jos H; Huitema, Alwin D R

    2008-10-01

    Indisulam and carboplatin have shown synergistic activity in preclinical studies. In a dose escalation study of the combination, a treatment delay was frequently required in a 3-weekly regimen to allow recovery from myelosuppression from previous cycles. A 4-weekly regimen was better tolerated, but had a decreased dose-intensity which may compromise efficacy. The aims of this study were (i) to develop a pharmacokinetic-pharmacodynamic (PK-PD) model to describe the myelosuppressive effect of the combination, and (ii) to use this model to select a dosing regimen for Phase II evaluation. Sixteen patients were treated at four different dose levels of indisulam (1-h infusion on day 1) and carboplatin (30-min infusion on day 2). Pharmacokinetic data were analysed with nonlinear mixed effects modelling. A semiphysiological model describing chemotherapy-induced myelosuppression characterized the relationship between the pharmacokinetics and the haematological toxicity of indisulam and carboplatin. A simulation study was performed to evaluate the tolerability and dose-intensity for 3-weekly and 4-weekly treatment regimens. The PK-PD model described the pharmacokinetics and the myelosuppressive effect of indisulam and carboplatin. The risk of a treatment delay at cycle 2 due to myelosuppression was unacceptably high (34-65%) in a 3-weekly regimen for various dose levels (350-600 mg m(-2) indisulam in combination with carboplatin to achieve an AUC of 4-6 mg min(-1) ml(-1)). This risk was acceptable for a 4-weekly regimen (9-24%), which is in line with the clinical study results. This PK-PD study supports the selection of indisulam 500 mg m(-2) and a dose of carboplatin to achieve an AUC of 6 mg min(-1) ml(-1) in a 4-weekly regimen as the recommended dose for future studies.

  19. A phase I study of combined radiation therapy with 5-fluorouracil and low dose folinic acid in patients with locally advanced pancreatic or biliary carcinoma

    International Nuclear Information System (INIS)

    Hsue, Victor; Shun, Wong C.; Moore, Malcolm; Erlichman, Charles; Cummings, Bernard J.; MacLeod, Marcia

    1996-01-01

    Purpose: To evaluate the toxicities of a Phase I study of radiation therapy with concurrent 5-fluorouracil (5FU) and low dose folinic acid in patients with locally advanced pancreatic or biliary carcinoma. Methods and Materials: Twenty-seven patients with locally advanced carcinoma of the pancreas (n = 19), bile duct (n = 7), and gall bladder (n = 1) were entered into a Phase I study of combined radiation therapy, 5FU, and folinic acid. Radiation was given as a split course of 40 Gy in 20 daily fractions with a gap of 2 weeks after 20 Gy. 5-Fluorouracil, 300 to 375 mg/m 2 /day and folinic acid, 20 mg/m 2 /day were given as an i.v. bolus daily for 5 days beginning on day 1 and again on day 29. Results: Eight patients developed Grade 3 or 4 toxicities (National Cancer Institute common toxicity criteria) including nausea and vomiting (n = 4), oral mucositis (n = 4), myelosuppression (n 2), infection (n = 2), and diarrhea (n = 1). Four patients did not complete the planned protocol due to treatment toxicities. There were two treatment deaths secondary to septic neutropenia. Treatment toxicity appeared to be related to age (> 70), performance status (ECOG = 2), and 5FU dose (> 350 mg/m 2 /day). Conclusion: This protocol is poorly tolerated by elderly patients or those with poor performance status, and 350 mg/m 2 /day is our recommended dose for 5FU as given in this protocol

  20. Treatment of Light Chain Deposition Disease Using Bortezomib-Based Regimen Followed by Thalidomide-Based Regimen in a Saudi Male

    Directory of Open Access Journals (Sweden)

    Bappa Adamu

    2016-01-01

    Full Text Available Light chain deposition disease (LCDD is a rare illness with, as yet, no clear evidence-based guidelines for its treatment. To the best of our knowledge, LCDD has not been previously reported from Saudi Arabia. We present in this report, a 38-year-old Saudi male who presented with clinical features suggestive of hypertensive nephropathy but kidney biopsy later revealed the diagnosis of LCDD. His serum creatinine at presentation was 297 μmol/L which came down to 194 μmol/L on treatment with Bortezomib, Cyclophosphamide and Dexamethasone. His 24-hour protein excretion at presentation was 6 g/L which also came down to less than 1 g/day. He was later placed on Cyclophosphamide, Thalidomide, and Dexamethasone regimen because of persistent high titres of serum free light chains. He went into remission with undetectable serum free light chains and remained so for three years at the time of writing this report. We conclude that LCDD, though rare, does occur in Saudi population. The treatment of LCDD is challenging but the use of Bortezomib, a proteosome inhibitor, is promising. However, suboptimal response may require further treatment with other therapeutic options such as chemotherapy with alkylating agents or high-dose Melphalan with autologous stem cell transplant.

  1. A randomized, controlled comparative study of the wrinkle reduction benefits of a cosmetic niacinamide/peptide/retinyl propionate product regimen vs. a prescription 0·02% tretinoin product regimen

    Science.gov (United States)

    Fu, JJJ; Hillebrand, GG; Raleigh, P; Li, J; Marmor, MJ; Bertucci, V; Grimes, PE; Mandy, SH; Perez, MI; Weinkle, SH; Kaczvinsky, JR

    2010-01-01

    Background Tretinoin is considered the benchmark prescription topical therapy for improving fine facial wrinkles, but skin tolerance issues can affect patient compliance. In contrast, cosmetic antiwrinkle products are well tolerated but are generally presumed to be less efficacious than tretinoin. Objectives To compare the efficacy of a cosmetic moisturizer regimen vs. a prescription regimen with 0·02% tretinoin for improving the appearance of facial wrinkles. Methods An 8-week, randomized, parallel-group study was conducted in 196 women with moderate to moderately severe periorbital wrinkles. Following 2 weeks washout, subjects on the cosmetic regimen (n=99) used a sun protection factor (SPF) 30 moisturizing lotion containing 5% niacinamide, peptides and antioxidants, a moisturizing cream containing niacinamide and peptides, and a targeted wrinkle product containing niacinamide, peptides and 0·3% retinyl propionate. Subjects on the prescription regimen (n=97) used 0·02% tretinoin plus moisturizing SPF 30 sunscreen. Subject cohorts (n=25) continued treatment for an additional 16 weeks. Changes in facial wrinkling were assessed by both expert grading and image analysis of digital images of subjects’ faces and by self-assessment questionnaire. Product tolerance was assessed via clinical erythema and dryness grading, subject self-assessment, and determinations of skin barrier integrity (transepidermal water loss) and stratum corneum protein changes. Results The cosmetic regimen significantly improved wrinkle appearance after 8 weeks relative to tretinoin, with comparable benefits after 24 weeks. The cosmetic regimen was significantly better tolerated than tretinoin through 8 weeks by all measures. Conclusions An appropriately designed cosmetic regimen can improve facial wrinkle appearance comparably with the benchmark prescription treatment, with improved tolerability. PMID:20374604

  2. A randomized, controlled comparative study of the wrinkle reduction benefits of a cosmetic niacinamide/peptide/retinyl propionate product regimen vs. a prescription 0.02% tretinoin product regimen.

    Science.gov (United States)

    Fu, J J J; Hillebrand, G G; Raleigh, P; Li, J; Marmor, M J; Bertucci, V; Grimes, P E; Mandy, S H; Perez, M I; Weinkle, S H; Kaczvinsky, J R

    2010-03-01

    Tretinoin is considered the benchmark prescription topical therapy for improving fine facial wrinkles, but skin tolerance issues can affect patient compliance. In contrast, cosmetic antiwrinkle products are well tolerated but are generally presumed to be less efficacious than tretinoin. To compare the efficacy of a cosmetic moisturizer regimen vs. a prescription regimen with 0.02% tretinoin for improving the appearance of facial wrinkles. An 8-week, randomized, parallel-group study was conducted in 196 women with moderate to moderately severe periorbital wrinkles. Following 2 weeks washout, subjects on the cosmetic regimen (n = 99) used a sun protection factor (SPF) 30 moisturizing lotion containing 5% niacinamide, peptides and antioxidants, a moisturizing cream containing niacinamide and peptides, and a targeted wrinkle product containing niacinamide, peptides and 0.3% retinyl propionate. Subjects on the prescription regimen (n = 97) used 0.02% tretinoin plus moisturizing SPF 30 sunscreen. Subject cohorts (n = 25) continued treatment for an additional 16 weeks. Changes in facial wrinkling were assessed by both expert grading and image analysis of digital images of subjects' faces and by self-assessment questionnaire. Product tolerance was assessed via clinical erythema and dryness grading, subject self-assessment, and determinations of skin barrier integrity (transepidermal water loss) and stratum corneum protein changes. The cosmetic regimen significantly improved wrinkle appearance after 8 weeks relative to tretinoin, with comparable benefits after 24 weeks. The cosmetic regimen was significantly better tolerated than tretinoin through 8 weeks by all measures. An appropriately designed cosmetic regimen can improve facial wrinkle appearance comparably with the benchmark prescription treatment, with improved tolerability.

  3. Combined homicide

    Directory of Open Access Journals (Sweden)

    Slović Živana

    2017-01-01

    Full Text Available Introduction: Combined homicide is a combination of two or more different modes of killing. These homicides occur when multiple perpetrators have different mode of killing, to hide the true manner of death, or when an initially unsuccessful attack with one weapon is abandoned and changed by another mode which is more successful, or due to availability of weapons at the scene of homicide, or unexpected appearance of possible eyewitness, or else. Case report: This case report is about 65-year old woman who was found in her residence on the floor next to the bed lying on her back with two kitchen knives in her neck. Autopsy revealed an abrasion on the frontal part of the neck and a bruise of the soft tissues of the neck with a double fracture of both greater horns of the hyoid bone and a fracture of both superior horns of the thyroid cartilage. The cause of death was exsanguination into right half of the thoracic cavity from the left subclavian artery which was cut, on the spot of stab wound in the neck. Conclusion: Hemorrhage in the soft tissue near broken hyoid bone and thyroid cartilage indicate that the victim was first strangulated and then stabbed with kitchen knives. Combined homicides are caused by one or more killers in order to accelerate the killing, or to be sure to provide the fatal outcome. This case is also interesting because the killer left weapon in the victim's neck.

  4. Impairments in timing, temporal memory, and reversal learning linked to neurotoxic regimens of methamphetamine intoxication.

    Science.gov (United States)

    Cheng, Ruey-Kuang; Etchegaray, Mikel; Meck, Warren H

    2007-12-01

    Methamphetamine intoxication has long-term consequences on dopaminergic function and corticostriatal-mediated behaviors in humans and other animals. In order to determine the potential impact on timing and temporal memory, we examined methamphetamine dose regimens that have been linked to neurotoxicity in adult (8 months) male rats. Rats that were given repetitive, high-dose methamphetamine (3.0 mg/kg ip x 4 injections/2 h) or saline injections were trained on a 2-s vs 8-s bisection procedure using auditory and visual signal durations. Following the high-dose regimen, baseline timing performance was reestablished prior to the rats' receiving reversal training in which the spatial/temporal mapping of the anchor durations (2 s and 8 s) to response options (left or right lever) was reversed. Low-dose methamphetamine (0.5 mg/kg ip) or saline injections were subsequently used to evaluate the effectiveness of the neurotoxic doses in terms of modifying the horizontal leftward shifts associated with increases in clock speed. Overall, the results indicate that MAP intoxication leads to reduced auditory/visual differences in clock speed, deficits in reversal learning, distortions in temporal memory, and lowered dopaminergic regulation of clock speed consistent with damage to prefrontal cortex and corticostriatal circuitry.

  5. A meal replacement regimen improves blood glucose levels in prediabetic healthy individuals with impaired fasting glucose.

    Science.gov (United States)

    König, Daniel; Kookhan, Sadaf; Schaffner, Denise; Deibert, Peter; Berg, Aloys

    2014-01-01

    The aim of this study was to investigate the effect of a 6-wk intervention with either lifestyle intervention (increased physical activity and a low-calorie diet) or a meal replacement regimen on glycemic control in patients who are prediabetic and have impaired fasting glucose. Forty-two overweight or obese men and women (age 54 ± 8 y; weight 95.1 ± 11.9 kg; body mass index [BMI] 32.8 ± 2.89 kg/m(2)) were included in this randomized controlled clinical trial. Patients in the lifestyle group (LS; n = 14) received dietary counseling sessions (fat-restricted low-calorie diet) and instructions on how to increase physical activity. Patients in the meal replacement group (MR; n = 28) were instructed to replace two daily meals with a low-calorie, high soy-protein drink with a low glycemic index. Both interventions resulted in a significant decrease in body weight and BMI, although the reduction was more pronounced (P meal replacement is an effective intervention for rapid improvement of elevated fasting glucose and increased insulin concentrations, these being important biomarkers of the prediabetic state. The 6-wk intervention has shown that the effect of meal replacement on fasting blood glucose was comparable to the effect of lifestyle intervention. The alterations in BMI, insulin, and HOMA-IR were significantly more pronounced following the meal replacement regimen. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. HIV drug resistance in infants increases with changing prevention of mother-to-child transmission regimens.

    Science.gov (United States)

    Poppe, Lisa K; Chunda-Liyoka, Catherine; Kwon, Eun H; Gondwe, Clement; West, John T; Kankasa, Chipepo; Ndongmo, Clement B; Wood, Charles

    2017-08-24

    The objectives of this study were to determine HIV drug resistance (HIVDR) prevalence in Zambian infants upon diagnosis, and to determine how changing prevention of mother-to-child transmission (PMTCT) drug regimens affect drug resistance. Dried blood spot (DBS) samples from infants in the Lusaka District of Zambia, obtained during routine diagnostic screening, were collected during four different years representing three different PMTCT drug treatment regimens. DNA extracted from dried blood spot samples was used to sequence a 1493 bp region of the reverse transcriptase gene. Sequences were analyzed via the Stanford HIVDRdatabase (http://hivdb.standford.edu) to screen for resistance mutations. HIVDR in infants increased from 21.5 in 2007/2009 to 40.2% in 2014. Nonnucleoside reverse transcriptase inhibitor resistance increased steadily over the sampling period, whereas nucleoside reverse transcriptase inhibitor resistance and dual class resistance both increased more than threefold in 2014. Analysis of drug resistance scores in each group revealed increasing strength of resistance over time. In 2014, children with reported PMTCT exposure, defined as infant prophylaxis and/or maternal treatment, showed a higher prevalence and strength of resistance compared to those with no reported exposure. HIVDR is on the rise in Zambia and presents a serious problem for the successful lifelong treatment of HIV-infected children. PMTCT affects both the prevalence and strength of resistance and further research is needed to determine how to mitigate its role leading to resistance.

  7. The effect of treatment regimens for vaginitis and cervicitis on vaginal colonization by lactobacilli.

    Science.gov (United States)

    Agnew, K J; Hillier, S L

    1995-01-01

    The goal of this study was to determine the effect of various treatment regimens on vaginal colonization by H2O2-positive and H2O2-negative lactobacilli. The subset of women enrolled in a large longitudinal cohort study who had Chlamydia trachomatis (n = 13), bacterial vaginosis (n = 105), yeast vaginitis (n = 15), or mucopurulent cervicitis (n = 47) were compared with 93 women without genital infection from the same population. The effect of various treatment regimens on lactobacilli was evaluated. Use of doxycycline, azithromycin, clotrimazole, and fluconazole had little effect on vaginal colonization by Lactobacillus. Use of oral or vaginal metronidazole led to an increase in Lactobacillus, which persisted 1 month after therapy. Intravaginal clindamycin use caused a decrease 1 week post-therapy, but at 1 month, levels of lactobacilli were similar to those in the metronidazole treatment group. Women treated with oral ampicillin had a modest increase in Lactobacillus levels. Use of antimicrobial agents for treating vaginitis and cervicitis do not cause a decrease in vaginal colonization by Lactobacillus, which is detectable 1 week to 1 month after treatment.

  8. Involved field radiation therapy for Hodgkin's disease autologous bone marrow transplantation regimens

    International Nuclear Information System (INIS)

    Pezner, Richard D.; Nademanee, Auayporn; Niland, Joyce C.; Vora, Nayana; Forman, Stephen J.

    1995-01-01

    From 1986 through 1992, involved-field radiation therapy (IF-RT) was administered to 29 of 86 patients with recurrent Hodgkin's disease (HD) who received a high-dose cyclophosphamide/etoposide regimen with autologous bone marrow transplantation (A-BMT). Patients without a significant history of prior RT received total body irradiation (TBI), initially as a single dose 5-7.5 Gy, and subsequently with fractionated TBI (F-TBI) delivering 12 Gy. Previously irradiated patients received a high-dose BCNU regimen instead of TBI. IF-RT was employed selectively, usually for sites of bulky disease (> 5 cm). IF-RT doses were typically 20 Gy at 2 Gy per fraction for TBI patients and 30-40 Gy at 1.8-2.0 Gy per fraction for non-TBI Patients. Fatal complications developed in four patients while second malignancies have developed in two. The region which received IF-RT was the site of first recurrence in only two cases (7%). With a median follow-up of 28 months, the two-year disease-free survival rate was 44%. For the 22 patients treated by either F-TBI or high-dose BCNU, the 2-year disease-free survival rate was 50% with a median follow up of 29 months. Selective use of IF-RT may increase the chances of complete remission and disease free survival in HD patients with a history of bulky disease

  9. Comparison of different regimens of pimecrolimus 1% cream in the treatment of facial seborrheic dermatitis.

    Science.gov (United States)

    Zhao, Juemin; Sun, Wenjia; Zhang, Chengfeng; Wu, Jiaqiang; Le, Yan; Huang, Chunyun; Liu, Ye; Xiang, Leihong

    2018-02-01

    Pimecrolimus 1% cream has already been proved to be an effective and safe alternative to treat seborrheic dermatitis. However, the treatment periods were inconstant in previous studies. To evaluate the comparative efficacy of pimecrolimus 1% cream with different regimens for the treatment of facial seborrheic dermatitis. Thirty patients with facial seborrheic dermatitis were enrolled and randomly distributed to three groups. Patients of Group 1 were treated with topical pimecrolimus cream 1% twice daily for 2 weeks and then a moisturizer cream twice daily for 2 weeks. Patients of Group 2 were treated with pimecrolimus cream 1% twice daily for 2 weeks and then once daily for another 2 weeks. Patients of Group 3 had a consecutive course of pimecrolimus cream 1% twice daily for 4 weeks. Objective symptoms, subjective symptoms, and dermatology life quality index (DLQI) were measured at weeks 0, 2, 4, and 6. At week 4, the clinical severity scores of all three regimens significantly decreased (Pseborrheic dermatitis. © 2017 Wiley Periodicals, Inc.

  10. The efficacy of two oral hygiene regimens in reducing oral malodour: a randomised clinical trial.

    Science.gov (United States)

    Feres, Magda; Figueiredo, Luciene Cristina; Faveri, Marcelo; Guerra, Marcelo C; Mateo, Luis R; Stewart, Bernal; Williams, Malcolm; Panagakos, Foti

    2015-12-01

    This study compared the efficacy of two oral hygiene regimens in reducing oral malodour and the proportions of bacterial species involved in the production of volatile sulphur compounds. Seventy subjects who participated in a halitosis-induction phase and achieved an organoleptic score of ≥ 3.0 [time point 0 (T0)] randomised into two groups: brushing with regular fluoride toothpaste alone (control group) or brushing with regular fluoride toothpaste followed by rinsing with a 0.075% cetylpyridinium chloride (CPC) mouthwash (CPC group). Subjects followed their assigned oral hygiene regimen for 21 days. Then, they underwent an organoleptic examination and measurement of volatile sulphur compounds (VSCs) using a portable gas chromatograph, 12 hours after their last oral hygiene procedure (T1) and 4 hours after an on-site oral hygiene (T2). Microbiological samples (supragingival biofilm, tongue coating and saliva) were analysed using checkerboard DNA-DNA hybridisation. Both therapies statistically significantly improved the organoleptic scores (P oral malodour scores were reduced by 49% at the 4-hour assessment (T2) compared with those not rinsing (P oral malodour, measured organoleptically and instrumentally, and in the proportions of red-complex species when compared with brushing alone. © 2015 FDI World Dental Federation.

  11. Different Nebulized Budesonide Dosing Regimens in a Mouse Model of Chronic Asthma

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    Pınar Uysal

    2016-12-01

    Full Text Available Objective: The aim of this study was to compare the effectiveness of different inhaled steroid regimens on the lungs and their potential side effects on the bone tissues in chronic asthma model. Materials and Methods: Thirty-five specific pathogen-free BALB/c mice were divided into five groups. The mice in all of the study groups except the control group were sensitized with chicken egg albumin. After sensitization, the mice in group 2 were treated with saline modeling twice daily, the mice in group 3 were treated with 250 mcg of nebulized budesonide twice daily, the mice in group 4 were treated with 500 mcg of budesonide once daily, and the mice in group 5 were treated with 1000 mcg of budesonide every other day for the last 14 days of the challenge period. After challenge, the mice were sacrificed and lung and tibia samples were histologically examined. Results: Pulmonary parameters, including subepithelial smooth muscle thickness, goblet cell count, mast cell count and epithelial thickness, were the lowest in group 5 compared to other groups (p0.01. Conclusion: The beneficial effect on lung tissue was highest in the treatment group receiving budesonide every other day (group 5 and no further measureable side effects on bone mineralization were observed in this group compared with the other treatment groups. Every-other-day treatment application seems to be the most effective regimen in chronic asthma model.

  12. Antibiotic regimen based on population analysis of residing persister cells eradicates Staphylococcus epidermidis biofilms

    Science.gov (United States)

    Yang, Shoufeng; Hay, Iain D.; Cameron, David R.; Speir, Mary; Cui, Bintao; Su, Feifei; Peleg, Anton Y.; Lithgow, Trevor; Deighton, Margaret A.; Qu, Yue

    2015-01-01

    Biofilm formation is a major pathogenicity strategy of Staphylococcus epidermidis causing various medical-device infections. Persister cells have been implicated in treatment failure of such infections. We sought to profile bacterial subpopulations residing in S. epidermidis biofilms, and to establish persister-targeting treatment strategies to eradicate biofilms. Population analysis was performed by challenging single biofilm cells with antibiotics at increasing concentrations ranging from planktonic minimum bactericidal concentrations (MBCs) to biofilm MBCs (MBCbiofilm). Two populations of “persister cells” were observed: bacteria that survived antibiotics at MBCbiofilm for 24/48 hours were referred to as dormant cells; those selected with antibiotics at 8 X MICs for 3 hours (excluding dormant cells) were defined as tolerant-but-killable (TBK) cells. Antibiotic regimens targeting dormant cells were tested in vitro for their efficacies in eradicating persister cells and intact biofilms. This study confirmed that there are at least three subpopulations within a S. epidermidis biofilm: normal cells, dormant cells, and TBK cells. Biofilms comprise more TBK cells and dormant cells than their log-planktonic counterparts. Using antibiotic regimens targeting dormant cells, i.e. effective antibiotics at MBCbiofilm for an extended period, might eradicate S. epidermidis biofilms. Potential uses for this strategy are in antibiotic lock techniques and inhaled aerosolized antibiotics. PMID:26687035

  13. Heterologous Prime-Boost HIV-1 Vaccination Regimens in Pre-Clinical and Clinical Trials

    Directory of Open Access Journals (Sweden)

    Julia L. Hurwitz

    2010-02-01

    Full Text Available Currently, there are more than 30 million people infected with HIV-1 and thousands more are infected each day. Vaccination is the single most effective mechanism for prevention of viral disease, and after more than 25 years of research, one vaccine has shown somewhat encouraging results in an advanced clinical efficacy trial. A modified intent-to-treat analysis of trial results showed that infection was approximately 30% lower in the vaccine group compared to the placebo group. The vaccine was administered using a heterologous prime-boost regimen in which both target antigens and delivery vehicles were changed during the course of inoculations. Here we examine the complexity of heterologous prime-boost immunizations. We show that the use of different delivery vehicles in prime and boost inoculations can help to avert the inhibitory effects caused by vector-specific immune responses. We also show that the introduction of new antigens into boost inoculations can be advantageous, demonstrating that the effect of ‘original antigenic sin’ is not absolute. Pre-clinical and clinical studies are reviewed, including our own work with a three-vector vaccination regimen using recombinant DNA, virus (Sendai virus or vaccinia virus and protein. Promising preliminary results suggest that the heterologous prime-boost strategy may possibly provide a foundation for the future prevention of HIV-1 infections in humans.

  14. Body friendly, safe and effective regimen of MgSO4 for eclampsia

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    Gautam S. Aher, Urmila Gavali

    2013-01-01

    Full Text Available Pre-eclampsia and eclampsia are major health problems in developing countries. MgSO4 is the standard drug in the control of convulsions in eclampsia. Our study carried out at PDVVPF’s hospital is based on the low dose regimen than Pritchard, which is suitable for Indian women who are of smaller built thanwomen in western world. This prospective study included 50 eclampsia patients receiving low dose MgSO4 therapy. The loading dose of MgSO4 was 9gm. Following this 2.5 gm was given intramuscularly every 6 hourly for 24 hours after administration of the loading dose. Patients were monitored hourly by observing their respiratory rate, knee jerk and urine output. Out of 50, two patients required Pritchard regimen, rest completely recovered from eclampsia. The maternal and perinatal morbidity and mortality were comparable to those of the standard Pritchard regime. The study did not find a single case of magnesium related toxicity with low dose MgSO4 regime. Low dose magnesium sulphate regime was found to be safe and effective in eclampsia

  15. Tonometers and infectious risk: myth or reality? Efficacy of different disinfection regimens on tonometer tips.

    Science.gov (United States)

    Cillino, S; Casuccio, A; Giammanco, G M; Mammina, C; Morreale, D; Di Pace, F; Lodato, G

    2007-04-01

    To evaluate the adequacy of common disinfection regimens for disposable tonometer tips and assess if disinfection of reusable prisms or the use of disposable tips is preferable. We used disposable tonometer tips, using the same material and tip diameter of standard Goldmann tonometer prism. Strains of Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilisand Candida albicanswere tested according to the European standard guidelines for disinfectants test. Antimicrobial effectiveness of the following disinfection practices has been assessed: dry wipe, Minuten wipes (Alpro), soaking in 3% hydrogen peroxide, 0.5% benzalkonium chloride, and 0.5% Pantasept for 1, 5, and 15 min. All tests have been performed three times and all conditions tested in duplicate. Dry wiping and 1 min soak in 3% hydrogen peroxide were ineffective on all microrganisms. Minuten wipes, 1 min soak in 0.5% benzalkonium chloride or 3% hydrogen peroxide were ineffective on B. subtilis. 0.5% Pantasept soak was effective in 1 min for all microrganisms tested, whereas 3% hydrogen peroxide and 0.5% benzalkonium chloride soaks were effective when performed for at least 5 min. B. subtiliswas the most resistant organism to disinfectant regimes at 1 min time. Results of our study demonstrate a relative disinfection efficacy for the different evaluated regimens, provided that correct exposure times are adopted for the chosen disinfectants, a condition difficult to ensure in a busy clinic setting. We conclude that disposable prism tonometry provides a safe alternative to Goldmann tonometry.

  16. Single Tablet Regimen Usage and Efficacy in the Treatment of HIV Infection in Australia

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    B. Armstrong

    2015-01-01

    Full Text Available Single tablet regimens (STRs for HIV infection improve patient satisfaction, quality of life, medication adherence, and virological suppression compared to multitablet regimens (MTRs. This is the first study assessing STR uptake and durability in Australia. This retrospective audit of all patients receiving an STR (n=299 at a large Sydney HIV clinic (January 2012–December 2013 assessed patient demographics, treatment prior to STR, HIV RNA load and CD4 during MTR and STR dosing, and reasons for STR switch. 206 patients switched from previous antiretroviral treatment to an STR, of which 88% switched from an MTR. Reasons for switching included desire to simplify treatment (57%, reduced side effects or toxicity (18%, and cost-saving for the patient. There was no switching for virological failure. Compared to when on an MTR, patients switching to an STR had significantly lower HIV RNA counts (p<0.001 and significantly higher CD4 counts (p<0.001. The discontinuation rate from STR was very low and all patients who switched to an STR maintained virological suppression throughout the study duration, although the study is limited by the absence of a control group.

  17. Novel agents and regimens for acute myeloid leukemia: 2009 ASH annual meeting highlights

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    Zhu Xiongpeng

    2010-04-01

    Full Text Available Abstract Prognostic markers, such as NPM1, Flt3-ITD, and cytogenetic abnormalities have made it possible to formulate aggressive treatment plans for unfavorable acute myeloid leukemia (AML. However, the long-term survival of AML with unfavorable factors remains unsatisfactory. The latest data indicate that the standard dose of daunorubicin (DNR at 45 mg/m2 is inferior to high dose 90 mg/m2 for induction therapy. The rates of complete remission and overall survival are significantly better in the high dose induction regimen. New regimens exploring the new liposomal encapsulation of Ara-C and DNR as well as addition of gemtuzumab ozogamicin monoclonal antibody have been studied. New agents, including the nucleoside analogues (clofarabine, sapacitabine, elacytarabine, FLT3 inhibitor (sorafenib, farnesyl-transferase inhibitor (tipifarnib, histone deacetylase inhibitor (vorinostat, lenalidomide, as well as DNA methyltransferase inhibitors (decitabine, azacitidine, were recently reported for AML treatment in the 2009 ASH annual meeting. This review also summarizes the updates of the clinical trials on novel agents including voreloxin, AS1413, behenoylara-C, ARRY520, ribavirin, AZD1152, AZD6244, and terameprocol (EM-1421 from the 2009 ASH annual meeting.

  18. Current regimen of pulse therapy for pemphigus: Minor modifications, improved results

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    Pasricha J

    2008-01-01

    Full Text Available Background: If administered properly, dexamethasone cyclophosphamide pulse (DCP therapy has the potential to effect lifelong recovery from pemphigus. Aims: The objective of this paper is to highlight various parameters of DCP therapy and also, to report the effects of a few modifications in the regimen. Methods: An analysis of 123 patients treated with the DCP/DP regimen over a period of five years (1998 to 2002 is presented here. Seventeen patients who did not start/continue the treatment and three patients who died during the treatment have been excluded from the analysis. Twenty patients who had not yet started families were given only dexamethasone pulses (DPs while 103 patients received DCPs. Low dose (50 mg/day cyclophosphamide was used as in the standard regimen. The three modifications introduced into the regimen were: (1 an additional daily dose of oral betamethasone sufficient to control the disease activity during phase I, which was progressively tapered off completely as the patient recovered, (2 use of systemic antibiotics if the patient had skin lesions, and oral anti-candida drugs if the patient had oral ulcers until complete healing, and (3 insistence on thorough cleaning of the skin and scalp with a normal soap and shampoo, and proper maintenance of oral hygiene in spite of skin/mucosal lesions. The regimen consisted of DCP/DP repeated in exactly 28-day cycles, along with 50 mg cyclophosphamide per day, insistence on completing the treatment and avoiding irregular pulses in all patients. The number of DCPs/DPs during phase I varied in different patients depending upon the dose of betamethasone used and the rate of recovery, but phase II (nine DCPs/DPs in exactly 28-day cycles along with 50 mg cyclophosphamide per day and phase III (only 50 mg cyclophosphamide per day was fixed at nine months each. This was followed by posttreatment follow-up (phase IV. Results: At present, all the patients are in complete remission. The

  19. Economic Outcomes of First-Line Regimen Switching Among Stable Patients with HIV.

    Science.gov (United States)

    Rosenblatt, Lisa; Buikema, Ami R; Seare, Jerry; Bengtson, Lindsay G S; Johnson, Jonathan; Cao, Feng; Villasis-Keever, Angelina

    2017-07-01

    Although switching of antiretroviral therapy (ART) is a valid approach for addressing treatment failure in patients with human immunodeficiency virus (HIV), ART changes among those who are well maintained on their current regimens may lead to the development of new side effects or resistance. To examine the effect of first-line regimen switching on subsequent health care utilization and cost among stable HIV patients. This was a retrospective claims data study of adult patients with HIV who initiated ART between 2007 and 2013 and had been treated with their initial regimens for at least 6 continuous months. Those with evidence of pregnancy or HIV-2 were excluded. Patients who underwent an ART change were assigned to a switcher cohort; a nonswitcher cohort was then generated by matching up to 20 nonswitchers for each switcher, with replacement. The index date was the date of the first ART change for switchers and was the claim date closest to the corresponding switcher's switch date for nonswitchers. Patient characteristics at baseline and post-index annualized health care utilization and costs were analyzed descriptively and with multivariable models. Analyses were performed in the full population and among patients designated as virologically stable (had undetectable viral ribonucleic acid [RNA] for 90 days pre-index) and virologically and clinically stable (had undetectable viral RNA and no apparent clinical reason for switching ART). The study population consisted of 6,983 individuals, which included 927 switchers (168 virologically stable; 55 virologically+clinically stable), who were matched with replacement with 18,511 nonswitcher comparators. The switcher cohort was 88.8% male (mean age 43.8 years). Mean preindex and follow-up treatment durations for switchers and nonswitchers were 1.8 years and 1.5 years, respectively; demographic characteristics, pre-index treatment duration, and follow-up duration were similar between cohorts. Significantly more

  20. Survival of HIV/AIDS patients with antiretroviral therapy in association with first-line regimens from 2007 – 2010 in Haji AdamMalik general hospital Medan

    Science.gov (United States)

    Kembaren, T.; Ginting, Y.; Saragih, R. H.

    2018-03-01

    The mortality related to AIDS have decreased dramatically among HIV infected patients taking HAART. HAART is the combination of at least 3 antiretroviral drugs based on the recommendation of WHO. The recent guideline for 1st line therapy recommended by the Indonesian Ministry of Health was Zidovudine/Lamivudine/Nevirapine (ZDV+3TC+NVP), Zidovudine/Lamivudine/Efavirenz (ZDV+3TC+EFV), Stavudine/Lamivudine/Nevirapine (d4T+3TC+NVP), Stavudine/Lamivudine/Efavirenz (d4T+3TC+EFV). Due to a side effect of Stavudine, Ministry of Health plan to pass out Stavudin from the regimens for 1stline therapy.We wanted to evaluate the survival of HIV/AIDS patients with first-line regimens in HAM general hospital Medan. A cohort retrospective study was conducted to evaluate the survival of HIV/AIDS patients taking a combination of 1st line antiretroviral therapy between January 2007 and December 2010. From 2007-2010, among 609 HIV/AIDS patients with first-line ARV medication, 77.5% were male, and 22.5% were female. The most common risk infection was heterosexual. The majority of the patients were in 25-34 years old group. Most of the patients with CD4 1-50 cell/mm3. 2 years survival rate in HIV/AIDS patients taking ZDV+3TC+NVP, ZDV+3TC+EFV, d4T+3TC+NVP, d4T+3TC+EFV were 61.5%, 61.2%, 57.5% and 59.3% respectively. There were no significant differences of 24 months survival in both regiment with or without d4T, 61.8% vs 63.6%.

  1. Changing Trend of Empirical Antibiotic Regimen: Experience of Two Studies at Different Periods in a Neonatal Intensive Care Unit in Tehran, Iran

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    Asghar Marzban

    2010-09-01

    Full Text Available "nBacterial sepsis is one of the most common causes of mortality and morbidity in neonates. It has been recognized a gradual change in spectrum of organisms responsible for neonatal sepsis. In this study we have evaluated changing trend of incidence and antibiotic susceptibility in neonatal late - onset sepsis (LOS in 2-periods. This study is based on results of blood culture in neonatal late-onset sepsis, in 2--periods study throughout 12 - years. Neonatal LOS was defined as clinical signs suggestive of infection with a positive blood culture (B/C after 72 hrs of birth. During first study (period: 1990-1992, the most common bacteremia in LOS was staphylococcus aureus (staph aureus (34%. Overall gram- negative bacteria (GNB were the predominant organism (66%. It was shown that 60% of GNB were resisted to gentamicin and 3% to amikacin, while in case of gram-positive bacteria (GPB; about 95% were resisted to ampicillin and 28% to cephalothin. In the second study (period: 2004-2007, the vast majority (56.6% of septic cases were caused by GNB. The most common cause of late- onset sepsis was klebsiela p. (31%. The GPB were resistant to cephalothin (90%. There has been a dramatic increase resistance to cephalothin and aminoglycosides and 3rd -generation cephalosporins. The combination of cephalothin plus amikacin in suspected LOS was no longer the effective therapeutic regimen in our neonatal intensive care unit (NICU. Now, it seems the best choice for empiric antibiotic regimen in suspected LOS is the combination vancomycin plus amikacin. Constant surveillance is important to guide empirical antibiotic therapy and changes in trends.

  2. High Virologic Failure Rates with Maraviroc-Based Salvage Regimens Among Indian Patients: A Preliminary Analysis-Maraviroc Effectiveness in HIV-1 Subtype C.

    Science.gov (United States)

    Pujari, Sanjay; Gaikwad, Sunil; Bele, Vivek; Joshi, Kedar; Dabhade, Digamber

    2018-01-01

    There is no information on the clinical effectiveness of Maraviroc (MVC) amongst People Living with HIV (PLHIV) in India infected with HIV-1 Subtype C viruses. We conducted a retrospective chart review of adult PLHIV on MVC based Antiretroviral (ARV) regimens for at least 6 months. Maraviroc was initiated amongst PLHIV with documented R5 tropic viruses (determined by in-house population sequencing of the V3 loop in triplicate and interpreted using the Geno2Pheno algorithm) in combination with an Optimized Background regimen (designed using genotypic resistance testing and past ARV history). Plasma viral loads (PVL) are performed 6 months post-initiation and annually thereafter. Primary outcome d. Median duration on MVC treatment was 1.8 years (range 1-2.9 years) while median duration of ART prior to switching to MVC was 13 years. Maraviroc was combined with Darunavir/ritonavir (DRV/r) (n=10), Atazanavir/r (ATV/r) (n=2) and Lopinavir/r (LPV/r) (n=1). All PLHIV were infected with HIV-1 Subtype C. Only 23.3% PLHIV achieved virologic suppression at 6 months and sustained it for 2.3 years. Median CD4 count change from baseline was +117 (n=13), +228 (n=10), +253 (n=9), and +331 (n=4) at 6, 12, 18 and 24 months respectively. Repeat tropism among patients with virologic failure demonstrated R5 virus. High rates of virologic failure was seen when MVC was used amongst treatment experienced PLHIV infected with HIV-1 Subtype C in India. was the proportion of PLHIV with virologic success (PVL<50 copies/ml) at last follow up visit. Data on 13 PLHIV were analyze.

  3. Changing trend of empirical antibiotic regimen: experience of two studies at different periods in a neonatal intensive care unit in Tehran, Iran.

    Science.gov (United States)

    Marzban, Asghar; Samaee, Hadi; Mosavinasab, Noredien

    2010-01-01

    Bacterial sepsis is one of the most common causes of mortality and morbidity in neonates. It has been recognized a gradual change in spectrum of organisms responsible for neonatal sepsis. In this study we have evaluated changing trend of incidence and antibiotic susceptibility in neonatal late - onset sepsis (LOS) in 2-periods. This study is based on results of blood culture in neonatal late-onset sepsis, in 2--periods study throughout 12 - years. Neonatal LOS was defined as clinical signs suggestive of infection with a positive blood culture (B/C) after 72 hrs of birth. During first study (period: 1990-1992), the most common bacteremia in LOS was staphylococcus aureus (staph aureus) (34%). Overall gram- negative bacteria (GNB) were the predominant organism (66%). It was shown that 60% of GNB were resisted to gentamicin and 3% to amikacin, while in case of gram-positive bacteria (GPB); about 95% were resisted to ampicillin and 28% to cephalothin. In the second study (period: 2004-2007), the vast majority (56.6%) of septic cases were caused by GNB. The most common cause of late- onset sepsis was klebsiela p. (31%). The GPB were resistant to cephalothin (90%). There has been a dramatic increase resistance to cephalothin and aminoglycosides and 3rd -generation cephalosporins. The combination of cephalothin plus amikacin in suspected LOS was no longer the effective therapeutic regimen in our neonatal intensive care unit (NICU). Now, it seems the best choice for empiric antibiotic regimen in suspected LOS is the combination vancomycin plus amikacin. Constant surveillance is important to guide empirical antibiotic therapy and changes in trends.

  4. Changing Trend of Empirical Antibiotic Regimen: Experience of Two Studies at Different Periods in a Neonatal Intensive Care Unit in Tehran, Iran

    Directory of Open Access Journals (Sweden)

    Asghar Marzban

    2010-10-01

    Full Text Available Bacterial sepsis is one of the most common causes of mortality and morbidity in neonates. It has been recognized a gradual change in spectrum of organisms responsible for neonatal sepsis. In this study we have evaluated changing trend of incidence and antibiotic susceptibility in neonatal late - onset sepsis (LOS in 2-periods. This study is based on results of blood culture in neonatal late-onset sepsis, in 2--periods study throughout 12 - years. Neonatal LOS was defined as clinical signs suggestive of infection with a positive blood culture (B/C after 72 hrs of birth. During first study (period: 1990-1992, the most common bacteremia in LOS was staphylococcus aureus (staph aureus (34%. Overall gram- negative bacteria (GNB were the predominant organism (66%. It was shown that 60% of GNB were resisted to gentamicin and 3% to amikacin, while in case of gram-positive bacteria (GPB; about 95% were resisted to ampicillin and 28% to cephalothin. In the second study (period: 2004-2007, the vast majority (56.6% of septic cases were caused by GNB. The most common cause of late- onset sepsis was klebsiela p. (31%. The GPB were resistant to cephalothin (90%. There has been a dramatic increase resistance to cephalothin and aminoglycosides and 3rd -generation cephalosporins. The combination of cephalothin plus amikacin in suspected LOS was no longer the effective therapeutic regimen in our neonatal intensive care unit (NICU. Now, it seems the best choice for empiric antibiotic regimen in suspected LOS is the combination vancomycin plus amikacin. Constant surveillance is important to guide empirical antibiotic therapy and changes in trends.

  5. Effectiveness of modified hyper-CVAD chemotherapy regimen in the treatment of adult acute lymphoblastic leukemia: a retrospective experience.

    Science.gov (United States)

    Jalaeikhoo, Hasan; Rajaeinejad, Mohsen; Keyhani, Manoutchehr; Zokaasadi, Mohammad; Dehghani Firoozabadi, Mohammad Mehdi

    2018-03-01

    Several chemotherapy regimens have been developed for the treatment of acute lymphoblastic leukemia (ALL), but relapse still presents the most common obstacles to attaining long-term survival. The hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and prednisolone)/HD MTX and Ara-C (high-dose methotrexate and cytarabine) chemotherapy regimen was first started in the MD Anderson Cancer Center as an intensive regimen for adult patients with ALL. The purpose of this study was to evaluate the effectiveness of a modified hyper-CVAD protocol. We used hyper-CVAD as consolidation/maintenance after remission induction with daunorubicin, vincristine, and prednisolone (and cyclophosphamide for T-cell ALL only) rather than standard hyper-CVAD in order to reduce treatment complications. This study was conducted as a retrospective review of medical records of ALL patients at 501 army hospital, Tehran, Iran, from 2005 to 2015. Three hundred and one patients underwent modified hyper-CVAD chemotherapy regimen. Complete remission and overall survival (OS) rates were measured as primary endpoints. Two hundred and forty-six (81.7%) reached complete remission (CR) during the first 6 months of treatment, and 55 patients (18.3%) did not reach CR. The 5-year OS rate was 51.8% (95% CI (confidence interval): 45.1-57.8%). Modified hyper-CVAD regimen is an efficient intensive chemotherapy regimen for consolidation/maintenance of adults with newly diagnosed ALL and has an acceptable 5-year overall that is comparable to standard hyper-CVAD regimen. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  6. Randomized clinical trial comparing fixed-time split dosing and split dosing of oral Picosulfate regimen for bowel preparation.

    Science.gov (United States)

    Jun, Jae Hyuck; Han, Koon Hee; Park, Jong Kyu; Seo, Hyun Il; Kim, Young Don; Lee, Sang Jin; Jun, Baek Gyu; Hwang, Min Sik; Park, Yoon Kyoo; Kim, Myeong Jong; Cheon, Gab Jin

    2017-08-28

    To compare the efficacy of fixed-time split dose and split dose of an oral sodium picosulfate for bowel preparation. This is study was prospective, randomized controlled study performed at a single Institution (2013-058). A total of 204 subjects were assigned to receive one of two sodium picosulfate regimens ( i.e ., fixed-time split or split) prior to colonoscopy. Main outcome measurements were bowel preparation quality and subject tolerability. There was no statistical difference between the fixed-time split dose regimen group and the split dose regimen group (Ottawa score mean 2.57 ± 1.91 vs 2.80 ± 2.51, P = 0.457). Cecal intubation time and physician's satisfaction of inspection were not significantly different between the two groups ( P = 0.428, P = 0.489). On subgroup analysis, for afternoon procedures, the fixed-time split dose regimen was equally effective as compared with the split dose regimen (Ottawa score mean 2.56 ± 1.78 vs 2.59 ± 2.27, P = 0.932). There was no difference in tolerability or compliance between the two groups. Nausea was 21.2% in the fixed-time split dose group and 14.3% in the split dose group ( P = 0.136). Vomiting was 7.1% and 2.9% ( P = 0.164), abdominal discomfort 7.1% and 4.8% ( P = 0.484), dizziness 1% and 4.8% ( P = 0.113), cold sweating 1% and 0% ( P = 0.302) and palpitation 0% and 1% ( P = 0.330), respectively. Sleep disturbance was two (2%) patients in the fixed-time split dose group and zero (0%) patient in the split dose preparation ( P = 0.143) group. A fixed-time split dose regimen with sodium picosulfate is not inferior to a split dose regimen for bowel preparation and equally effective for afternoon colonoscopy.

  7. The potential biomarkers in predicting pathologic response of breast cancer to three different chemotherapy regimens: a case control study

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    Xu Chaoyang

    2009-07-01

    Full Text Available Abstract Background Preoperative chemotherapy (PCT has become the standard of care in locally advanced breast cancer. The identification of patient-specific tumor characteristics that can improve the ability to predict response to therapy would help optimize treatment, improve treatment outcomes, and avoid unnecessary exposure to potential toxicities. This study is to determine whether selected biomarkers could predict pathologic response (PR of breast tumors to three different PCT regimens, and to identify a subset of patients who would benefit from a given type of treatment. Methods 118 patients with primary breast tumor were identified and three PCT regimens including DEC (docetaxel+epirubicin+cyclophosphamide, VFC (vinorelbine/vincristine+5-fluorouracil+cyclophosphamide and EFC (epirubicin+5-fluorouracil+cyclophosphamide were investigated. Expression of steroid receptors, HER2, P-gp, MRP, GST-pi and Topo-II was evaluated by immunohistochemical scoring on tumor tissues obtained before and after PCT. The PR of breast carcinoma was graded according to Sataloff's classification. Chi square test, logistic regression and Cochran-Mantel-Haenszel assay were performed to determine the association between biomarkers and PR, as well as the effectiveness of each regimen on induction of PR. Results There was a clear-cut correlation between the expression of ER and decreased PR to PCT in all three different regimens (p p Conclusion ER is an independent predictive factor for PR to PCT regimens including DEC, VFC and EFC in primary breast tumors, while HER2 is only predictive for DEC regimen. Expression of PgR, Topo-II, P-gp, MRP and GST-pi are not predictive for PR to any PCT regimens investigated. Results obtained in this clinical study may be helpful for the selection of appropriate treatments for breast cancer patients.

  8. A method for optimizing dosage regimens in oncology by visualizing the safety and efficacy response surface: analysis of inotuzumab ozogamicin.

    Science.gov (United States)

    Luu, Kenneth T; Boni, Joseph

    2016-10-01

    The aim of this investigation was to develop a quantitative method to optimize inotuzumab ozogamicin (InO) dosage regimen in patients with indolent non-Hodgkin lymphoma (NHL) by simultaneously balancing safety and efficacy. Pharmacokinetics (PK), safety and efficacy data were obtained from a phase 2 trial of InO administered intravenously to patients (n = 81) with indolent NHL. The PK was described by a two-compartment model which was linked to: (1) an exponential tumor growth model to describe tumor size time course (efficacy determinant expressed as objective response rate) and (2) a precursor-dependent platelet inhibition model to describe platelet time course (safety determinant expressed as thrombocytopenia grade). The model was used to simulate virtual trials to construct safety and efficacy response surfaces. Using the simulated safety and efficacy contours, a clinical utility index (CUI) contour was then constructed, from which optimal InO regimens were then selected. The model-simulated efficacy response surface indicated near-optimal efficacy of InO at the dosage regimen used in the trial (1.8 mg/m(2) every 4 weeks). The model-simulated safety response surface indicated that modifying the dosage regimen resulted in modest improvements in safety with little compromise in efficacy. The CUI contour identified 2 mg/m(2) every 10, 11, or 12 weeks as the "sweet spot" for optimal InO dosage regimen in patients with indolent NHL. An approach to dosage regimen optimization was developed for simultaneously balancing safety and efficacy. This approach allows objective identification of optimal dosage regimens from early trial information and thus has broad utility across oncology trials.

  9. A bladder preservation regimen using intra-arterial chemotherapy and radiotherapy for invasive bladder cancer. A prospective study

    International Nuclear Information System (INIS)

    Miyanaga, Naoto; Akaza, Hideyuki; Okumura, Toshiyuki

    2000-01-01

    A prospective study was performed to investigate combined treatment with intra-arterial chemotherapy and radiation therapy for bladder preservation in locally invasive bladder cancer. Patients with invasive bladder cancer, stage T2-3N0M0, were included in the study. lntra-arterial chemotherapy was performed with three injections of methotrexate and cisplatin at 3-week intervals. Simultaneously, the patients underwent X-ray irradiation (40 Gy) of the small pelvic space. Where a post-treatment transurethral resection (TUR) biopsy showed no residual tumor, the tumor site was irradiated by a 30 Gy proton beam and the bladder was preserved. Where tumors remained, radical cystectomy was performed. Between 1990 and 1996, 42 patients were treated according to this protocol. Post-treatment TUR biopsy and urine cytology showed no residual tumors in 39 of 42 cases (93%). The bladder was preserved in accordance with the study protocol in 36 cases. A median follow-up of 38 months showed 3-year non-recurrence in 72% of bladder-preserved patients and the rate of bladder preservation was 84%. The nine recurrences included eight cases of superficial bladder recurrence. One cancer death occurred among the bladder-preservation patients, giving 3-year survival and cause-specific survival rates of 84% and 100%, respectively. Although bladder function decreased slightly in compliance, bladder capacity was retained in almost all cases. This regimen is useful for bladder preservation in T2-3 locally invasive bladder cancer. Information from more cases and the results of more long-term observations are needed, as is an evaluation of appropriate subject selection and factors associated with quality of life issues, particularly regarding bladder function. (author)

  10. Antiplatelet Regimen for Patients With Breakthrough Strokes While on Aspirin: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Lee, Meng; Saver, Jeffrey L; Hong, Keun-Sik; Rao, Neal M; Wu, Yi-Ling; Ovbiagele, Bruce

    2017-09-01

    Optimal antiplatelet therapy after an ischemic stroke or transient ischemic attack while on aspirin is uncertain. We, therefore, conducted a systematic review and meta-analysis. We searched PubMed (1966 to August 2016) and bibliographies of relevant published original studies to identify randomized trials and cohort studies reporting patients who were on aspirin at the time of an index ischemic stroke or transient ischemic attack and reported hazard ratio for major adverse cardiovascular events or recurrent stroke associated with a switch to or addition of another antiplatelet agent versus maintaining aspirin monotherapy. Estimates were combined using a random effects model. Five studies with 8723 patients with ischemic stroke or transient ischemic attack were identified. Clopidogrel was used in 4 cohorts, and ticagrelor was used in 1 cohort. Pooling results showed that addition of or a switch to another antiplatelet agent, versus aspirin monotherapy, was associated with reduced risks of major adverse cardiovascular events (hazard ratio, 0.68; 95% confidence interval, 0.54-0.85) and recurrent stroke (hazard ratio, 0.70; 95% confidence interval, 0.54-0.92). Each of the strategies of addition of and switching another antiplatelet agent showed benefit versus continued aspirin monotherapy, and studies with regimen initiation in the first days after index event showed more homogenous evidence of benefit. Among patients who experience an ischemic stroke or transient ischemic attack while on aspirin monotherapy, the addition of or a switch to another antiplatelet agent, especially in the first days after index event, is associated with fewer future vascular events, including stroke. © 2017 American Heart Association, Inc.

  11. The impact of the new antiviral regimens on patient reported outcomes and health economics of patients with chronic hepatitis C.

    Science.gov (United States)

    Younossi, Zobair; Henry, Linda

    2014-12-15

    Hepatitis C is an important cause of chronic liver disease worldwide with an estimated 170 million people infected. Hepatitis C virus (HCV)-infected patients are physically and mentally impacted by fatigue, depression and anxiety causing an impairment of health related quality of life (HRQOL), lower worker productivity and other patient reported outcomes (PROs). Although anti-HCV regimens containing first generation direct acting antiviral agents (DAAs) were associated with significant side effects, the second generation DAAs, sofosbuvir (SOF) and simeprevir (SMV), are associated with fewer side effects, better tolerability and high cure rates. Despite these advantages, key stakeholders are currently trying to find ways to best integrate these new therapeutic regimens into the management of patients with chronic hepatitis C for the benefit of all. The purpose of this article is to offer insight into the other key and equally important outcomes (PRO's, HRQOL and cost) which should be considered when assessing the applicability of these new regimens for the care of patients infected with HCV. Our review provides evidence that the new treatment regimens for HCV not only have high efficacy rates but are also associated with better patient reported outcomes and cost per case of HCV cured. Additionally, compared to other medical interventions, these new regimens are cost-effective from a societal perspective. Copyright © 2014. Published by Elsevier Ltd.

  12. A phase II study of V-BEAM as conditioning regimen before second auto-SCT for multiple myeloma.

    Science.gov (United States)

    Wang, T-F; Fiala, M A; Cashen, A F; Uy, G L; Abboud, C N; Fletcher, T; Wu, N; Westervelt, P; DiPersio, J F; Stockerl-Goldstein, K E; Vij, R

    2014-11-01

    High-dose melphalan has been the standard conditioning regimen for auto-SCT in multiple myeloma (MM) for decades. A more effective conditioning regimen may induce deeper responses and longer remission duration. It is especially needed in the setting of second auto-SCT, which rarely achieves comparable results with the first auto-SCT using the same conditioning regimen. Here we conducted a phase II study to investigate the efficacy and safety of a conditioning regimen V-BEAM (bortezomib-BEAM) before second auto-SCT for multiple myeloma. Ten patients were enrolled from September 2012 to May 2013. The CR rate at day +100 after auto-SCT was 75%; all except for one patient remained in remission after a median follow-up of 6 months. Three patients developed Clostridium difficile infection. Two patients died within the first 30 days of auto-SCT from neutropenic colitis and overwhelming sepsis, respectively. Due to the high rate of morbidity and mortality, the study was terminated after 10 patients. In summary, although the conditioning regimen V-BEAM before second auto-SCT for MM provided promising responses, it was associated with unexpected treatment-related toxicity and should not be investigated further without modifications.

  13. Beneficial effects of an alternating high- fat dietary regimen on systemic insulin resistance, hepatic and renal inflammation and renal function.

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    Gopala K Yakala

    Full Text Available BACKGROUND: An Alternating high- cholesterol dietary regimen has proven to be beneficial when compared to daily high- cholesterol feeding. In the current study we explored whether the same strategy is applicable to a high- fat dietary regimen. OBJECTIVE: To investigate whether an alternating high- fat dietary regimen can effectively diminish insulin resistance, hepatic and renal inflammation and renal dysfunction as compared to a continuous high- fat diet. DESIGN: Four groups of male ApoE*3Leiden mice (n=15 were exposed to different diet regimens for 20 weeks as follows: Group 1: low- fat diet (10 kcal% fat; Group 2: intermediate- fat diet (25 kcal% fat; Group 3: high- fat diet (45 kcal% fat and Group 4: alternating- fat diet (10 kcal% fat for 4 days and 45 kcal% fat for 3 days in a week. RESULTS: Compared to high fat diet feeding, the alternating and intermediate- fat diet groups had reduced body weight gain and did not develop insulin resistance or albuminuria. In addition, in the alternating and intermediate- fat diet groups, parameters of tissue inflammation were markedly reduced compared to high fat diet fed mice. CONCLUSION: Both alternating and intermediate- fat feeding were beneficial in terms of reducing body weight gain, insulin resistance, hepatic and renal inflammation and renal dysfunction. Thus beneficial effects of alternating feeding regimens on cardiometabolic risk factors are not only applicable for cholesterol containing diets but can be extended to diets high in fat content.

  14. EXIT STRATEGY IN A TREAT-AND-EXTEND REGIMEN FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

    Science.gov (United States)

    Arendt, Petra; Yu, Siqing; Munk, Marion R; Ebneter, Andreas; Wolf, Sebastian; Zinkernagel, Martin S

    2017-11-17

    To evaluate the outcome of an exit strategy in a treat-and-extend regimen for neovascular age-related macular degeneration. Five hundred and ninety-eight eyes of 488 patients with neovascular age-related macular degeneration receiving intravitreal anti-vascular endothelial growth factor injections according to a treat-and-extend regimen were included in this retrospective study. A treat-and-extend regimen with either interval extension by 2 weeks or shortening by 1 week was used. "Exit criteria" were defined as 3 consecutive injections 16 weeks apart with stable findings after which the patient was exited from treatment and followed up at 3 to 4 monthly intervals without therapy. Best-corrected visual acuity, central retinal thickness at treatment initiation and termination, incidence of recurrence after treatment termination, presence of characteristics in the optical coherence tomography, duration of therapy, number and intervals of injections were analyzed. Seventeen percent of all included eyes met the exit criteria. The mean number of anti-vascular endothelial growth factor injections was 23.7 ± 14.7 with a mean treatment duration of 4.5 ± 2.5 years. Twelve percent reached exit with the minimal number of injections. Thirteen percent had recurrent disease after a mean of 37 ± 16 weeks. In the subgroup with recurrent disease, rate of pigment epithelial detachment at treatment termination was significantly higher than without recurrence (77% vs. 30%, P = 0.0018) with a significant higher proportion of serous pigment epithelial detachment (31% vs. 7%, P = 0.0247). The high percentage of patients meeting the exit criteria and the relatively low incidence of recurrences underline the usefulness of a predefined exit strategy. However, in a subgroup of patients, continuation of therapy may be advisable.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is

  15. Efficacy of 7-Day and 14-Day Triple Therapy Regimens for the Eradication of Helicobacter pylori: A Comparative Study in a Cohort of Romanian Patients

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    Stefan Sorin Arama

    2016-01-01

    Full Text Available Objective. This study compared the eradication rates of of Helicobacter pylori (HP infection by a 7-day and 14-day anti-HP regimen. Materials and Methods. An open, randomized, prospective study was performed to evaluate the response to anti-HP treatment in adult HP-positive patients following a 7-day course (Regimen A of a proton pump inhibitor in association with clarithromycin and amoxicillin compared to a 14-day course (Regimen B. Gastric biopsies were performed at baseline and two months after anti-HP treatment. Results. Seventy-eight patients aged 18–64 years (28 males, 50 females diagnosed with HP infection were included. Fifty-two (66.7% patients received Regimen B and 26 (33.3% Regimen A. The overall eradication rate was 70.5%. Better treatment response (p<0.01 was seen in Regimen B (44/52, 84.2% versus 11/26, 42.3%. Significant improvement in histological features was seen in regimen B. There has been significant overall reduction in endoscopic aspects of gastric and duodenal lesions in both regimens. Younger patients ≤35 years had a better response to Regimen B. Better treatment response was seen in women, urban residents, and those with tertiary level of education in both groups. Conclusion. 14-day anti-HP regimen offered a significant better overall eradication of HP in study population.

  16. Pretreatment serum human chorionic gonadotropin cutoff value for medical treatment success with single-dose and multi-dose regimen of methotrexate in tubal ectopic pregnancy.

    Science.gov (United States)

    Kim, Junhwan; Jung, Young Mi; Lee, Da Yong; Jee, Byung Chul

    2017-01-01

    To investigate individual pretreatment serum human chorionic gonadotropin (hCG) cutoff value for medical treatment success with single-dose and multi-dose regimen of methotrexate in tubal ectopic pregnancy. Eighty-five women who received methotrexate for the treatment of tubal ectopic pregnancy during 2003 to 2015 were selected. Fifty-three women received a single-dose regimen and 32 women received a multi-dose regimen. Medical treatment failure was defined as necessity of surgical treatment. The medical treatment success rate was estimated in both regimens and the pretreatment serum hCG titer to predict the success was assessed by receiver operating characteristics curve analysis. Pretreatment clinical and laboratory parameters were similar between group of single-dose regimen and multi-dose regimen. Treatment success rate was 64.2% in the single-dose regimen group and 71.9% in the multi-dose regimen group ( P >0.05). Pretreatment serum hCG titer was an independent prognostic factor for treatment success in each regimen. Serum hCG cutoff value to predict the treatment success was 3,026 IU/L in single-dose regimen group and 3,711 IU/L in multi-dose regimen group. We recommend use of single-dose regimen when pretreatment serum hCG <3,026 IU/L but multi-dose regimen may be favored when initial serum hCG level between 3,026 and 3,711 IU/L.

  17. Switching from pro re nata to treat-and-extend regimen improves visual acuity in patients with neovascular age-related macular degeneration.

    Science.gov (United States)

    Kvannli, Line; Krohn, Jørgen

    2017-11-01

    To evaluate the visual outcome after transitioning from a pro re nata (PRN) intravitreal injection regimen to a treat-and-extend (TAE) regimen for patients with neovascular age-related macular degeneration (AMD). A retrospective review of patients who were switched from a PRN regimen with intravitreal injections of bevacizumab, ranibizumab or aflibercept to a TAE regimen. The best corrected visual acuity (BCVA), central retinal thickness (CRT) and type of medication used at baseline, at the time of changing treatment regimen and at the end of the study were analysed. Twenty-one eyes of 21 patients met the inclusion criteria. Prior to the switch, the patients received a mean of 13.8 injections (median, 10; range, 3-39 injections) with the PRN regimen for 44 months (range, 3-100 months), which improved the visual acuity in five patients (24%). After a mean of 6.1 injections (median, 5; range, 3-14 injections) with the TAE regimen over 8 months (range, 2-16 months), the visual acuity improved in 12 patients (57%). The improvement in visual acuity during treatment with the TAE regimen was statistically significant (p = 0.005). The proportion of patients with a visual acuity of 0.2 or better was significantly higher after treatment with the TAE regimen than after treatment with the PRN regimen (p = 0.048). No significant differences in CRT were found between the two treatment regimens. Even after prolonged treatment and a high number of intravitreal injections, switching AMD patients from a PRN regimen to a strict TAE regimen significantly improves visual acuity. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  18. Evaluation of skin firmness by the DynaSKIN, a novel non-contact compression device, and its use in revealing the efficacy of a skincare regimen featuring a novel anti-ageing ingredient, acetyl aspartic acid.

    Science.gov (United States)

    Kearney, E M; Messaraa, C; Grennan, G; Koeller, G; Mavon, A; Merinville, E

    2017-05-01

    One of the key strategies for anti-ageing in the cosmetics industry today is to target the structural changes responsible for ptosis of the skin, given its impact on age perception. Several objective and non-invasive methods are available to characterise the biomechanical properties of the skin, which are operator-dependent, involving skin contact and providing single-dimensional numerical descriptions of skin behaviour. The research introduces the DynaSKIN, a device using non-contact mechanical pressure in combination with fringe projection to quantify and visualise the skin response in 3-dimensions. We examine the age correlation of the measurements, how they compare with the Cutometer ® , and measure skin dynamics following application of a skincare regimen containing established anti-ageing ingredients. DynaSKIN and Cutometer ® measurements were made on the cheek of 80 Caucasian women (18-64 years). DynaSKIN volume, mean depth and maximum depth parameters were correlated with age and 15 Cutometer ® parameters. Subsequently, the firming efficacy of a skincare regimen featuring acetyl aspartic acid (AAA) and a peptide complex was examined in a cohort of 41 volunteers. DynaSKIN volume, mean depth and maximum depth parameters correlate with age and the Cutometer ® parameters that are associated with the skin relaxation phase (R1, R2, R4, R5, R7 and F3). Furthermore, the DynaSKIN captured significant improvements in skin firmness delivered by the skincare regimen. The DynaSKIN is a novel device capable of capturing skin biomechanics at a high level of specificity and successfully detected the firming properties of a skincare regimen. Its independent measuring principle, consumer relevance and skin firmness 3D visualisation capabilities bring objectivity and novelty to product efficacy substantiation evaluation. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Pharmacokinetics and Pharmacodynamics of Twice Daily and Once Daily Regimens of Empagliflozin in Healthy Subjects.

    Science.gov (United States)

    Macha, Sreeraj; Brand, Tobias; Meinicke, Thomas; Link, Jasmin; Broedl, Uli C

    2015-08-01

    This study was undertaken to compare the steady-state pharmacokinetic and pharmacodynamic properties of empagliflozin 5 mg twice daily (BID) and 10 mg once daily (QD) in healthy subjects. In an open-label, 2-way crossover study, subjects (n = 16) received empagliflozin 5 mg BID for 5 days and empagliflozin 10 mg QD for 5 days in a randomized order, with a washout period of ≥6 days between each treatment. The primary objective was the comparison of the overall exposure during a 24-hour period at steady state (AUC0-24,ss) for empagliflozin, based on standard bioequivalence criteria, with BID and QD dose regimens. The study population comprised 7 (43.8%) men and 9 (56.3%) women with a baseline median age of 38.0 years (range, 23-47 years) and a median body mass index of 23.3 kg/m(2) (range, 19.8-27.8 kg/m(2)). Based on standard bioequivalence criteria, there was no difference in the overall exposure of empagliflozin between BID and QD dose regimens (geometric mean ratio of AUC0-24,ss for empagliflozin 5 mg BID compared with empagliflozin 10 mg QD = 99.36%; 90% CI, 94.29-104.71). For empagliflozin 10 mg QD, mean (%CV) AUC during the dosing interval was 1900 nmol · h/L (20.6%), mean (%CV) Cmax,ss was 330 nmol/L (25.3%), and median (range) Tmax,ss was 1.0 hour (0.7-2.0 hours). For empagliflozin 5 mg BID, mean (%CV) AUC during the dosing interval was 1010 nmol · h/L (15.1%) and 867 nmol · h/L (18.6%) after the morning and evening dose, respectively, mean (%CV) Cmax,ss was 193 nmol/L (16.5%) and 120 nmol/L (21.0%), respectively, and median Tmax,ss was 1.0 hour (range, 0.7-2.0 hours) and 2.0 hours (range, 1.0-4.0 hours), respectively. The mean (%CV) cumulative amount of glucose excreted in urine during 24 hours was 52.1 g (32.1%) with empagliflozin 5 mg BID and 43.9 g (30.3%) with empagliflozin 10 mg QD. Adverse events were reported in six subjects (37.5%) receiving empagliflozin 5 mg BID and four (25.0%) receiving empagliflozin 10 mg QD. Headache was the most frequent

  20. Successful hematopoietic stem cell transplantation following a cyclophosphamide-containing preparative regimen with concomitant phenobarbital administration.

    Science.gov (United States)

    Weber, Catherine; Kasberg, Heather; Copelan, Edward

    2012-01-01

    Cyclophosphamide is an immunosuppressive agent and an anticancer prodrug which requires bioactivation catalyzed primarily by cytochrome P450 enzymes in order to be transformed into its active alkylating compounds. Concomitant administration of drugs known to inhibit or induce this enzyme system is a clinical concern. Herein, we present the case of a chronically ill 21-year-old patient who received high-dose cyclophosphamide, equine antithymocyte globulin (eATG), and total body irradiation (TBI) followed by an allogeneic hematopoietic stem cell transplant (HSCT) for severe aplastic anemia. Throughout her hospitalization, she continued to receive quadruple anticonvulsant therapy including phenobarbital for her long-standing seizure history. The preparative regimen was tolerated well aside from a hypersensitivity reaction to eATG, and minimal cyclophosphamide-related toxicities. Safe and effective administration of high-dose cyclophosphamide was possible with multidisciplinary care consisting of physician, nursing, pharmacy, neurology consultation, as well as social work and case management.

  1. South American Heart Transplantation Registry of patients receiving everolimus in their immunosuppressive regimens.

    Science.gov (United States)

    Bortman, G V; Ceruti, B; Ahualli, L; Colque, R; Amuchástegui, M; Sgrosso, J L; Muñoz, J; Vulcano, N; Burgos, C; Diez, F; Rodriguez, M C; Perrone, S V

    2010-01-01

    The increasing number of heart transplant recipients receiving immunosuppression with mammalian target of rapamycin inhibitors prompted the implementation of a South American Transplant Physicians Group to register these patients in a database. Everolimus (EVL) is a signal proliferation inhibition that reduces graft vascular disease when used de novo. Recently, its administration has expanded to subjects with resistant rejection or with side effects due to other immunosuppressive drugs (calcineurin inhibitors and/or steroids), allowing for better regulation of the immunosuppressive regimen. Herein we have shown the data collected from patients receiving EVL in ten South American Heart Transplant Centers. We have concluded that the administration of EVL is a useful adjunctive therapy that allows the reduction or suspension of other immunosuppressive drugs that caused unwanted side effects, without a loss of immunosuppressive efficacy, with manageable side effects, and constituting a valuable therapeutic option.

  2. Ahemeral light regimens test the photoperiodic threshold of the european starling (Sturnus vulgaris)

    Science.gov (United States)

    Schwab, R. G.

    1980-03-01

    Male European starlings (Sturnus vulgaris) were held for three consecutive photoperiod oscillations (ahemeral years) composed of 30-h day lengths, i.e., the “daily” light and dark each lasted three hours longer than under the natural daily photoperiod at latitude 38°N. These starlings had no gonad metamorphosis during the 45 actual months necessary to complete the three ahemeral photoperiod oscillations; nor did subsequent exposure to continuous illumination elicit gonad response. It is concluded that the daily duration of light and darkness (although certainly operant in controlling starling sexual cycles under temperate-zone photoperiod oscillations) is not the critical factor establishing a sexual cycle under the ahemeral regimen. Rather, it appears that this species must experience a daily duration of light of 12 hours or less (a definitive photoperiodic threshold) before photo-induction of a sexual cycle is possible.

  3. Successful Hematopoietic Stem Cell Transplantation Following a Cyclophosphamide-Containing Preparative Regimen with Concomitant Phenobarbital Administration

    Directory of Open Access Journals (Sweden)

    Catherine Weber

    2012-01-01

    Full Text Available Cyclophosphamide is an immunosuppressive agent and an anticancer prodrug which requires bioactivation catalyzed primarily by cytochrome P450 enzymes in order to be transformed into its active alkylating compounds. Concomitant administration of drugs known to inhibit or induce this enzyme system is a clinical concern. Herein, we present the case of a chronically ill 21-year-old patient who received high-dose cyclophosphamide, equine antithymocyte globulin (eATG, and total body irradiation (TBI followed by an allogeneic hematopoietic stem cell transplant (HSCT for severe aplastic anemia. Throughout her hospitalization, she continued to receive quadruple anticonvulsant therapy including phenobarbital for her long-standing seizure history. The preparative regimen was tolerated well aside from a hypersensitivity reaction to eATG, and minimal cyclophosphamide-related toxicities. Safe and effective administration of high-dose cyclophosphamide was possible with multidisciplinary care consisting of physician, nursing, pharmacy, neurology consultation, as well as social work and case management.

  4. A multimodality regimen for deep venous thrombosis prophylaxis in total knee arthroplasty.

    Science.gov (United States)

    Reitman, Richard D; Emerson, Roger H; Higgins, Linda L; Tarbox, Tiffera R

    2003-02-01

    Data indicate that deep venous thrombosis (DVT) occurs at the time of knee arthroplasty. Nevertheless, literature concerning DVT prophylaxis has only recently addressed this contention. This prospective study evaluated the efficacy of a perioperative prophylactic regimen. Between January 1996 and June 2001, 1,308 knees (964 surgeries) underwent total knee arthroplasty. Patients were treated routinely with intraoperative heparin (1000 units intravenous push before inflation of the tourniquet and 500 units at deflation), hypotensive epidural anesthesia (MAP 70-90), external pneumatic compression boots, and aspirin (325 mg, PO, BID for 6 weeks). Duplex venous ultrasonography was performed before discharge. DVT was detected in 4% of cases (1% proximal and 3% distal). Bleeding complications occurred in 1%, and perioperative medical complications occurred in 12%. Copyright 2003, Elsevier Science (USA). All rights reserved.

  5. Disturbance Of Sleep-Wake Regimen As Prognosis Criterion Of Gastroesophageal Reflux Disease Exacerbation

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    R.V. Lyakisheva

    2009-09-01

    Full Text Available The goal of the present research is to define correlation of disease exacerbation risk within the next month and sleep-wake regimen changes in patients with gastroesophageal reflux disease. 40 patients with remission have been examined three times a week to determine qualitative and quantitative indices of sleep characteristic. During the following month the dynamic examination of the mentioned group of patients has been carried out for the purpose of timely acute condition diagnostics. It has been revealed that disturbances of sleep indices, such as late falling asleep, long-term falling asleep, frequency of awakening and unpleasant dreams become unfavorable risk factors for the development of the next recurrence of gastroesophageal reflux disease during the nearest month, but the remission of this disease is significantly connected with falling asleep duration and awakening time.

  6. A comparison of different antibiotic regimens for the treatment of infective endocarditis.

    Science.gov (United States)

    Martí-Carvajal, Arturo J; Dayer, Mark; Conterno, Lucieni O; Gonzalez Garay, Alejandro G; Martí-Amarista, Cristina Elena; Simancas-Racines, Daniel

    2016-04-19

    Infective endocarditis is a microbial infection of the endocardial surface of the heart. Antibiotics are the cornerstone of treatment, but their use is not standardised, due to the differences in presentation, populations affected and the wide variety of micro-organisms that can be responsible. To assess the existing evidence about the clinical benefits and harms of different antibiotics regimens used to treat people with infective endocarditis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE Classic and EMBASE, LILACS, CINAHL and the Conference Proceedings Citation Index on 30 April 2015. We also searched three trials registers and handsearched the reference lists of included papers. We applied no language restrictions. We included randomised controlled trials assessing the effects of antibiotic regimens for treating possible infective endocarditis diagnosed according to modified Duke's criteria. We considered all-cause mortality, cure rates and adverse events as the primary outcomes. We excluded people with possible infective endocarditis and pregnant women. Three review authors independently performed study selection, 'Risk of bias' assessment and data extraction in duplicate. We constructed 'Summary of findings' tables and used GRADE methodology to assess the quality of studies. We described the included studies narratively. Four small randomised controlled trials involving 728 allocated/224 analysed participants met our inclusion criteria. These trials had a high risk of bias. Drug companies sponsored two of the trials. We were unable to pool the data due to the heterogeneity in outcome definitions and the different antibiotics used.The included trials compared the following antibiotic schedules. The first trial compared quinolone (levofloxacin) plus standard treatment (anti-staphylococcal penicillin (cloxacillin or dicloxacillin), aminoglycoside (tobramycin or netilmicin) and rifampicin) versus standard treatment

  7. N-acetylcysteine regimens for paracetamol overdose: Time for a change?

    Science.gov (United States)

    Wong, Anselm; Graudins, Andis

    2016-12-01

    Paracetamol overdose is one of the commonest pharmaceutical poisonings in the world. For nearly four decades, intravenous acetylcysteine regimens have been used to treat most patients successfully and prevent or mitigate hepatotoxicity. However, the rate of occurrence of adverse reactions to acetylcysteine is quite high, and there is a potential for these to be reduced. Recent studies show that distributing the loading-dose of acetylcysteine over the first few hours of treatment may decrease the incidence of adverse reactions. In addition, varying the duration of acetylcysteine administration may potentially benefit certain cohorts of poisoned patients, depending on their risk of developing hepatotoxicity. © 2016 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

  8. Novel and Effective Therapeutic Regimens for Helicobacter pylori in an Era of Increasing Antibiotic Resistance

    Science.gov (United States)

    Hu, Yi; Zhu, Yin; Lu, Nong-Hua

    2017-01-01

    Helicobacter pylori (H. pylori) is a common gastrointestinal bacterial strain closely associated with the incidence of chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. A current research and clinical challenge is the increased rate of antibiotic resistance in H. pylori, which has led to a decreased H. pylori eradication rate. In this article, we review recent H. pylori infection and reinfection rates and H. pylori resistance to antibiotics, and we discuss the pertinent treatments. A PubMed literature search was performed using the following keywords: Helicobacter pylori, infection, reinfection, antibiotic resistance, bismuth, proton pump inhibitors, vonoprazan, susceptibility, quintuple therapy, dual therapy, and probiotic. The prevalence of H. pylori has remained high in some areas despite the decreasing trend of H. pylori prevalence observed over time. Additionally, the H. pylori reinfection rate has varied in different countries due to socioeconomic and hygienic conditions. Helicobacter pylori monoresistance to clarithromycin, metronidazole or levofloxacin was common in most countries. However, the prevalence of amoxicillin and tetracycline resistance has remained low. Because H. pylori infection and reinfection present serious challenges and because H. pylori resistance to clarithromycin, metronidazole or levofloxacin remains high in most countries, the selection of an efficient regimen to eradicate H. pylori is critical. Currently, bismuth-containing quadruple therapies still achieve high eradication rates. Moreover, susceptibility-based therapies are alternatives because they may avoid the use of unnecessary antibiotics. Novel regimens, e.g., vonoprazan-containing triple therapies, quintuple therapies, high-dose dual therapies, and standard triple therapies with probiotics, require further studies concerning their efficiency and safety for treating H. pylori. PMID:28529929

  9. Novel and Effective Therapeutic Regimens for Helicobacter pylori in an Era of Increasing Antibiotic Resistance

    Directory of Open Access Journals (Sweden)

    Yi Hu

    2017-05-01

    Full Text Available Helicobacter pylori (H. pylori is a common gastrointestinal bacterial strain closely associated with the incidence of chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. A current research and clinical challenge is the increased rate of antibiotic resistance in H. pylori, which has led to a decreased H. pylori eradication rate. In this article, we review recent H. pylori infection and reinfection rates and H. pylori resistance to antibiotics, and we discuss the pertinent treatments. A PubMed literature search was performed using the following keywords: Helicobacter pylori, infection, reinfection, antibiotic resistance, bismuth, proton pump inhibitors, vonoprazan, susceptibility, quintuple therapy, dual therapy, and probiotic. The prevalence of H. pylori has remained high in some areas despite the decreasing trend of H. pylori prevalence observed over time. Additionally, the H. pylori reinfection rate has varied in different countries due to socioeconomic and hygienic conditions. Helicobacter pylori monoresistance to clarithromycin, metronidazole or levofloxacin was common in most countries. However, the prevalence of amoxicillin and tetracycline resistance has remained low. Because H. pylori infection and reinfection present serious challenges and because H. pylori resistance to clarithromycin, metronidazole or levofloxacin remains high in most countries, the selection of an efficient regimen to eradicate H. pylori is critical. Currently, bismuth-containing quadruple therapies still achieve high eradication rates. Moreover, susceptibility-based therapies are alternatives because they may avoid the use of unnecessary antibiotics. Novel regimens, e.g., vonoprazan-containing triple therapies, quintuple therapies, high-dose dual therapies, and standard triple therapies with probiotics, require further studies concerning their efficiency and safety for treating H. pylori.

  10. Viral load and clinical disease enhancement associated with a lentivirus cytotoxic T lymphocyte vaccine regimen

    Science.gov (United States)

    Mealey, Robert H.; Leib, Steven R.; Littke, Matt H.; Wagner, Bettina; Horohov, David W.; McGuire, Travis C.

    2009-01-01

    Effective DNA-based vaccines against lentiviruses will likely induce CTL against conserved viral proteins. Equine infectious anemia virus (EIAV) infects horses worldwide, and serves as a useful model for lentiviral immune control. Although attenuated live EIAV vaccines have induced protective immune responses, DNA-based vaccines have not. In particular, DNA-based vaccines have had limited success in inducing CTL responses against intracellular pathogens in the horse. We hypothesized that priming with a codon-optimized plasmid encoding EIAV Gag p15/p26 with co-administration of a plasmid encoding an equine IL-2/IgG fusion protein as a molecular adjuvant, followed by boosting with a vaccinia vector expressing Gag p15/p26, would induce protective Gag-specific CTL responses. Although the regimen induced Gag-specific CTL in four of seven vaccinated horses, CTL were not detected until after the vaccinia boost, and protective effects were not observed in EIAV challenged vaccinates. Unexpectedly, vaccinates had significantly higher viral loads and more severe clinical disease, associated with the presence of vaccine-induced CTL. It was concluded that 1.) further optimization of the timing and route of DNA immunization was needed for efficient CTL priming in vivo, 2.) co-administration of the IL-2/IgG plasmid did not enhance CTL priming by the Gag p15/p26 plasmid, 3.) vaccinia vectors are useful for lentivirus-specific CTL induction in the horse, 4.) Gag-specific CTL alone are either insufficient or a more robust Gag-specific CTL response is needed to limit EIAV viremia and clinical disease, and 5.) CTL-inducing vaccines lacking envelope immunogens can result in lentiviral disease enhancement. Although the mechanisms for enhancement associated with this vaccine regimen remain to be elucidated, these results have important implications for development of lentivirus T cell vaccines. PMID:19368787

  11. Efficacy assessment of two antibiotic prophylaxis regimens in oral and maxillofacial trauma surgery: preliminary results

    Science.gov (United States)

    Campos, Giordano BP; Lucena, Eudes ES; da Silva, José Sandro P; Gomes, Petrus P; Germano, Adriano R

    2015-01-01

    The study set out to evaluate the efficacy of two antibiotic prophylaxis regimens in patients with facial fractures admitted to the Oral and Maxillofacial Surgery and Traumatology services of the Onofre Lopes University Hospital attached to the Federal University of Rio Grande do Norte in the period from December 2011 to December 2012. The sample consisted of 74 patients divided into two groups, GI with forty-three patients and GII with 32. Both groups received 2 g of cefazolin, 20 minutes before surgery. The postoperative protocol for each group was randomly determined; group I (single dose) received no antibiotics after surgery but group II (24 h dosage) received 1 g of cefazolin every 6 hours for 24 hours. Postoperative infection incidence was 9.3% (seven patients), six patients in Group I and one in Group II. 85% of the infections were in mandibular fractures. Results were presented qualitatively and quantitatively and the Chi square test (taking the value for p to be < 0.05) showed no statistically significant differences in the efficacies of the two regimens in the comparisons made between the cases of fractures in the upper and middle thirds of the face with those in the lower third (mandibular fractures). Considering mandibular fractures alone, Group II proved to be more efficacious with a p value of 0.02. However, to confirm the tendency shown in the mandibular fracture treatments whereby prolonging antibiotic administration for 24 hours appeared to be beneficial, research needs to be done with much larger sample groups. PMID:25932244

  12. Efficacy of two regimens of dexamethasone for management of preterm labour: pilot study

    International Nuclear Information System (INIS)

    Rasool, A.; Farooq, U.

    2017-01-01

    Background: Dexamethasone is widely used for prevention of respiratory distress syndrome (RDS), necrotising enterocolitis (NEC) and intra-ventricular haemorrhage (IVH) in preterm babies; decreasing the neonatal mortality rate. There is no consensus on the dose of corticosteroid administered to the mother expected to have a preterm baby. This study is conducted to compare the effectiveness of two popular regimens of dexamethasone administration in decreasing incidence of RDS, necrotizing enterocolitis, IVH and neonatal mortality rate. Methods: Randomized control trial was conducted at Ayub Teaching Hospital, Abbottabad from 1st to 31st August, 2014. Sample size was set at 50. Block randomization was employed in the trial to allocate the patients into corresponding groups 'A' and 'B'. Group A was administered 6mg dexamethasone in 4 doses 12 hours apart and group B was administered 2 doses 12 hours apart. Results: Forty-eight patients participated in the study with 24 patients in each group. Mean age and period gestation of participants were 28.4 years±4.3 SD and 34 weeks±1.9 SD respectively. Four patients in group A gave birth to neonate with RDS compared to two cases in group B. Group B had higher incidence of necrotizing enterocolitis and neonatal mortalities. However, none of these differences observed were statistically significant. No case of IVH was reported in either of the groups. Conclusion: Both the popular regimens of dexamethasone administration are equally effective in decreasing the incidence of neonatal diseases. (author)

  13. Comparison of post cesarean infection after single dose versus three doses of prophylactic antibiotic regimen

    Directory of Open Access Journals (Sweden)

    Farnaz Mohammadian

    2013-04-01

    Full Text Available Background: Cesarean delivery is a surgical operation which is applied to prevent maternal and fetal complications. Cesarean delivery isn’t without complication and has some complications such as infection. Postoperative infection includes endometritis, wound infection and septic pelvic thrombophlebitis that depend to prophylactic antibiotics and surgical technique. The aim of this study was comparison of post operative infection after single dose and three doses of prophylactic antibiotic regimens. . Material and Methods: This double blind randomized clinical trial was performed on all pregnant women referd to the Vali-Asr Hospital of Zanjan University of Medical Sciences and underwent cesarean delivery during one year from starting study. Participants subsequently were randomized into two groups: A (recieved single dose of prophylactic antibiotic and B (recieved three doses of prophylactic antibiotic. Subjects were checked up for the clinical signs of infection during hospitalization and 10 days after discharge. The results were analyzed by SPSS Software Ver16 and Chi-Square Test. Results: During one year, 146 pregnant women with cesarean delivery entered 2 equal groups (A and B which each group had 73 subjects. During hospitalization after cesarean delivery, 5(6.8% patients of group A and 2(2.7% patients of group B had fever. There was no significant correlation between the two groups. Conclusion: There was no significant correlation between single dose and three doses of prophylactic antibiotic regimens in groups A and B. Therefore, it seems thatthere is no need to use three doses of prophylactic antibiotic for cesarean delivery.Therfore, because of drug resistance and economic loss, single dose of prophylactic antibiotic is recommended for prevention of post cesarean infection

  14. Erosion Potential of Tooth Whitening Regimens as Evaluated with Polarized Light Microscopy.

    Science.gov (United States)

    Brambert, Patrick; Qian, Fang; Kwon, So Ran

    2015-11-01

    Tooth whitening is a widely utilized esthetic treatment in dentistry. With increased access to over-the-counter (OTC) systems concerns have been raised as to potential adverse effects associated with overuse of whitening materials. Therefore, this study aimed to evaluate enamel erosion due to different whitening regimens when used in excess of recommended guidelines. Extracted human teeth (n = 66) were randomly divided into 11 groups (n = 6/group). Specimens were exposed to OTC products: Crest Whitestrips and 5-minute natural white and a do-it-yourself (DIY) strawberry whitening recipe. Within each regimen, groups were further divided per exposure time: specimens receiving the recommended product dosage; 5 times the recommended dosage; and 10 times the recommended dosage. Negative and positive controls were treated with grade 3 water and 1.0% citric acid, respectively. Specimens were nail-varnished to limit application to a 1 × 4 mm window. Following treatment, specimens were sectioned and erosion (drop in μm) measured using polarized light microscopy. Two-sample t-test was used to detect difference in amount of enamel erosion between negative and positive groups, while one-way analysis of variance (ANOVA), followed by post hoc Dunnett's test was used to detect difference between set of treatment groups and negative control groups or among all experimental groups. There was significant difference in mean amount of enamel erosion (p erosion for positive control group was significantly greater than that for negative control group (23.50 vs 2.65 μm). There was significant effect for type of treatments on enamel erosion [F(9,50) = 25.19; p 0.05 for all instances), except for Natural White_10 times treatment group (p erosion. Enamel erosion due to the overuse of whitening products varies for different modalities and products. Therefore, caution is advised when using certain over-the-counter products beyond recommended guidelines, as there is potential for enamel

  15. Single dose antibiotic therapy is not as effective as conventional regimens for management of acute urinary tract infections in children.

    Science.gov (United States)

    Madrigal, G; Odio, C M; Mohs, E; Guevara, J; McCracken, G H

    1988-05-01

    One hundred thirty-two children with acute urinary tract infection were randomly assigned to receive trimethoprim-sulfamethoxazole in one dose, two doses daily for 3 days or two doses daily for 7 days. The patient characteristics, etiologic agents and frequency of roentgenologic abnormalities were similar for the three treatment groups. There was no significant difference in bacteriologic cure rates for the single dose regimen (93%) and multidose regimens (96%). The difference in rates of recurrent urinary tract infection between the single dose (20.5%) and 3-day (5.6%) and 7-day (8%) regimens was statistically significant (P = 0.033). A single dose of trimethoprim-sulfamethoxazole is inadequate treatment for infants and children with acute urinary tract infection.

  16. Pharmacokinetic Profile of a 2-Month Dose Regimen of Aripiprazole Lauroxil: A Phase I Study and a Population Pharmacokinetic Model.

    Science.gov (United States)

    Hard, Marjie L; Mills, Richard J; Sadler, Brian M; Wehr, Angela Y; Weiden, Peter J; von Moltke, Lisa

    2017-07-01

    Aripiprazole lauroxil (AL) is a long-acting injectable medication approved for the treatment of schizophrenia. Current AL regimens are 441 mg, 662 mg, and 882 mg administered monthly (every 4 weeks [q4wk]), or 882 mg administered every 6 weeks (q6wk). We examined the feasibility of a 2-month (every 8 weeks [q8wk]) dosing interval of AL in a phase I open-label pharmacokinetic study investigating AL 1064 mg administered q8wk for 24 weeks, followed by 20 weeks of safety and pharmacokinetic measurements (ClinicalTrials.gov ID: NCT02320032). Second, a population pharmacokinetic model (referred to as the 2MPopPK model) was generated using data collected from the present trial, as well as data obtained from earlier studies. The phase I study included patients with schizophrenia or schizoaffective disorder maintained on an oral antipsychotic (n = 140) who were assigned to one of three groups: AL 441 mg q4wk, AL 882 mg q6wk, or AL 1064 mg q8wk, with a total of seven, five, or four injections administered, respectively. No oral aripiprazole lead-in supplementation was administered and patients continued on maintenance oral antipsychotics. Pharmacokinetic samples were collected at various time points during the 24-week study period and the 20-week follow-up period. Plasma concentrations obtained from the phase I study were analyzed using non-compartmental methods. Additionally, the data were combined with data collected from prior studies to develop the 2MPopPK model. Following the final injection of AL in the phase I study, maximum aripiprazole concentrations were achieved 24.4-35.2 days after the last dose and persisted for the duration of the study. The mean C avg,ss values were 125.8 ng/ml, 131.1 ng/ml, and 140.7 ng/ml for the 441 mg q4wk, 882 mg q6wk, and 1064 mg q8wk doses, respectively. The mean elimination half-life of aripiprazole following the last dose was 53.9 days for the 1064 mg dose, 55.1 days for the 882 mg dose, and 57.2 days for

  17. Randomized clinical trial of fluid and salt restriction compared with a controlled liberal regimen in elective gastrointestinal surgery.

    Science.gov (United States)

    Kalyan, J P; Rosbergen, M; Pal, N; Sargen, K; Fletcher, S J; Nunn, D L; Clark, A; Williams, M R; Lewis, M P N

    2013-12-01

    Excessive intravenous fluid prescription may play a causal role in postoperative complications following major gastrointestinal resectional surgery. The aim of this study was to investigate whether fluid and salt restriction would decrease postoperative complications compared with a more modern controlled liberal regimen. In this observer-blinded single-site randomized clinical trial consecutive patients undergoing major gastrointestinal resectional surgery were randomized to receive either a liberal control fluid regimen or a restricted fluid and salt regimen. The primary outcome was postoperative complications of grade II and above (moderate to severe). Some 240 patients (194 colorectal resections and 46 oesophagogastric resections) were enrolled in the study; 121 patients were randomized to the restricted regimen and 119 to the control (liberal) regimen. During surgery the control group received a median (interquartile range) fluid volume of 2033 (1576-2500) ml and sodium input of 282 (213-339) mmol, compared with 1000 (690-1500) ml and 142 (93-218) mmol respectively in the restricted group. There was no significant difference in major complication rate between groups (38·0 and 39·0 per cent respectively). Median (range) hospital stay was 8 (3-101) days in the controls and 8 (range 3-76) days among those who received restricted fluids. There were four in-hospital deaths in the control group and two in the restricted group. Substantial differences in weight change, serum sodium, osmolality and urine : serum osmolality ratio were observed between the groups. There were no significant differences in major complication rates, length of stay and in-hospital deaths when fluid restriction was used compared with a more liberal regimen. ISRCTN39295230 (http://www.controlled-trials.com). © 2013 The Authors. British Journal of Surgery published by John Wiley & Sons Ltd on behalf of British Journal of Surgery Society Ltd.

  18. Circulating Tumor Cell Enumeration in a Phase II Trial of a Four-Drug Regimen in Advanced Colorectal Cancer.

    Science.gov (United States)

    Krebs, Matthew G; Renehan, Andrew G; Backen, Alison; Gollins, Simon; Chau, Ian; Hasan, Jurjees; Valle, Juan W; Morris, Karen; Beech, Janette; Ashcroft, Linda; Saunders, Mark P; Dive, Caroline

    2015-06-01

    Multidrug regimens are active against advanced colorectal cancer (ACRC). However, the increased toxicity requires the use of biomarkers to select the patients who will derive the most benefit. We assessed circulating tumor cells (CTCs) as a prognostic biomarker in patients treated with a 4-drug regimen. A single-arm phase II trial (Erbitux Study of CPT11, Oxaliplatin, UFToral Targeted-therapy [eSCOUT]) was undertaken in patients with previously untreated KRAS wild-type ACRC using a regimen of irinotecan, oxaliplatin, and tegafur-uracil with leucovorin and cetuximab. Baseline CTCs were enumerated using CellSearch. The endpoints were an objective response rate (ORR) and overall survival (OS). We modeled our results and compared them with those modeled for the capecitabine, oxaliplatin, bevacizumab +/- cetuximab (CAIRO2) trial, stratifying patients a priori into low (< 3) and high (≥ 3) CTC groups. For 48 eligible patients, the best ORR from the 4-drug regimen was 71%, with a disease control rate of 98%. The median OS for patients with a high and low CTC count was 18.7 and 22.3 months (log-rank test, P = .038), respectively. In our modeled data, for patients with a low CTC count, no differences were found between the median OS in the eSCOUT trial and that in the CAIRO2 trial (22.2 vs. 22.0 months). However, for the high CTC group, a clinically relevant improvement was seen in median OS (eSCOUT vs. CAIRO2, 18.7 vs. 13.7 months; P = .001). These data are hypothesis generating-for patients with ACRC, stratification by CTC count can identify those who might benefit the most from an intensive 4-drug regimen, avoiding high-toxicity regimens in low CTC groups. This hypothesis warrants validation in a phase III biomarker-driven trial. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. The role of a low-dose ketamine-midazolam regimen in the management of severe painful crisis in patients with sickle cell disease.

    Science.gov (United States)

    Tawfic, Qutaiba A; Faris, Ali S; Kausalya, Rajini

    2014-02-01

    Acute pain is one of the main causes of hospital admission in sickle cell disease, with variable intensity and unpredictable onset and duration. We studied the role of a low-dose intravenous (IV) ketamine-midazolam combination in the management of severe painful sickle cell crisis. A retrospective analysis was performed with data from nine adult patients who were admitted to the intensive care unit with severe painful sickle cell crises not responding to high doses of IV morphine and other adjuvant analgesics. A ketamine-midazolam regimen was added to the ongoing opioids as an initial bolus of ketamine 0.25mg/kg, followed by infusion of 0.2-0.25mg/kg/h. A midazolam bolus of 1mg followed by infusion of 0.5-1mg/h was added to reduce ketamine emergence reactions. Reduction in morphine daily requirements and improvement in pain scores were the determinants of ketamine-midazolam effect. The t-tests were used for statistical analysis. Nine patients w